Daaru-Haridraa (Berberis aristata)

Daaru-Haridraa (Berberis aristata)

Introduction 
Daaru-Haridraa (AKA Barberry in the West), Berberis aristata occupied an important place in Ayurveda. In Ayurveda its pleiotropic properties were harnessed to treat a variety of ailments. In the Middle East Barberry (Berberis aristata) attained the status of “medicine” in ancient times, since Egyptian pharaohs and queens used Barberry with fennel seeds to prevent and ward off the plague. In Egypt it is still in vogue for fevers associated with pestilence. In the medieval times it was recommended for liver and gallbladder disorders. For many years, in Europe and America it has been used for the treatment of fever, disorders of the stomach, loss of appetite, diarrhea and to improve ‘energy’ and well being. In Russia it has been used for inflammations and high arterial tension. In Italy it is known as “Holy Thorn”. The Italians believe that the plant is wrapped in Christ’s thorns he wore around his skull. 
The philosophy of the “Doctrine of Signatures”, dating from the time of Dioscurides and Galen, states that, herbs that resemble various parts of the body can be used to treat ailments of that part of the body. A theological justification offered by botanists like William Coles for this philosophy was that God would have wanted to show men what plants would be useful for treating ailments of various parts of the body. “It was reasoned that the Almighty must have set his sign upon the various means of curing disease which he provided.” Since the wood of the tree Daaru-Haridraa AKA Barberry (Berberis aristata) is yellow in color, early physicians used it to treat jaundice. (Daaru stands for wood and Haridraa for yellow color resembling the color of Haridraa i. e. Turmeric) 
There is no scientific evidence to prove the “Doctrine of Signatures”. Scientists therefore see the doctrine as a superstition. [1]
Other Names 
Botanical: Berberis aristata
Sanskrit: Daaru-Haridraa, Daaru-Peetaa, (Peetaa-Daaru?), Darvi,   
English: Indian Berberry
Bengali: Daaruharidraa
Gujarati: Daaru-Haldar.
Hindi: Daaru-Haldee, Kashmal
Kannada: Daaruhaldi, Maradarishana, Maradarishina  
Kashmiri : Rassashud 
Malayalam : Maramanjal, Maramannal
Marathi: Daaru-Halad, Raswat
Oriya: Daaruhalidi, Daaruharidraa
Punjabi: Sumalu
Tamil: Gangeti, Varatiu manjal 
Telugu: Manupasupu
Urdu: Darhald  [2]

Taxonomic Classification 
Kingdom: Plantae
Unranked: Angiosperm
Unranked: Eudicots
Division: Magnoliophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Berberidaceae 
Berberis aristata also known as Indian Barberry or Tree Turmeric, belongs to the genus Berberis. The genus comprises of approximately 450-500 species of deciduous evergreen shrubs found in the temperate climate. The species commonly occur in central and southern Europe, the northeastern region of the US and in South Asia (northern area of Pakistan). Five species of this plant occur in Iran. [3], [4]
Geographical Distribution 
Berberis aristata is native to the Himalayas and Nepal. The herb also grows in Nilgiri range in Southern India. The shrub is found in the temperate and sub-tropical regions of Asia, Europe and America. Mostly it is found in Nepal and wet zone of Sri Lanka; grown in Nilgiris and all over temperate Himalayas. It is also said to be native to Europe. It is now naturalized and cultivated in North America. Now it is a common garden bush. It grows in the form of a deciduous shrub in almost any garden in Britain and Europe. It also grows in hard gravelly soils of northern US regions and in the rich soils of the Western states. It blossoms in mid-spring, to the beginning of summer.   
Berberis species, called “Zereshk” in Persian language, are widely cultivated in Iran, The South Khorasan province (especially around Birjand and Qaen) is the major field of cultivation for “Zereshk” in the world. [5], [6]

Plant Morphology
    
                                                                                                                                                            
                                                                                              The Plant

                                                                     

                                                                        The Roots


                                                       
                                                                    
                                                                       The Stem




                                                         


                                                                         The Leaves                                              



                                          

  
                                                                     The Flowers


                                      

                          

                  

                                                                   The Fruits
                                     Images of Daaruharidraa (Berberis aristata[7], [8]

Daaruharidraa is a large, deciduous, erect spiny shrub, growing in thick horny clumps reaching between 3 and 8 feet in height. The roots and stem are burgeoning (flourishing) with the potent alkaloid berberine, making its stems appear to be ‘Turmeric-colored’ hence its name: Daaru-Haridraa [9]
Macroscopic 
Root is cylindrical, yellow in color, thick, woody, covered with a thin brittle bark; more or less knotty, much branched, externally light yellowish brown, longitudinally wrinkled and scaly, fracture hard and tough.
Stem is red when the plant is young, getting darker as the plant grows older, from 3 to 8 feet in height. The twigs are whitish to pale yellowish brown in color; available in pieces of variable length and thickness 
Bark is about 0.4 to 0.8 cm thick woody, soft pale yellow to brown outside and deep yellow inside, covered with three branched thorns which are modified leaves, and can be peeled by hand in longitudinal strips. 
Leaves are arranged in tufts of 5 to 8, obovate, approximately 5 cm long and 2 cm broad, simple, deep green in color on the dorsal and light green on the ventral surface, leathery in texture, toothed, with several indentations along the margin.   
Flowers are complete, hermaphrodite and yellow in color. They form a racemose inflorescence with 11 to 16 flowers per raceme, arranged along a central stem. The flowers have 3 large and 3 small sepals, 6 petals; androecium (the male reproductive structure) contains 6 stamens and are 6 mm long    
The plant flowers between March and April. 
Fruits are edible berries, succulent, bright red in color, ovoid, smooth, acidic when raw, have medicinal properties. The berries are 7 mm long and 4 mm in diameter. They start ripening from the second week of May and continue to do so throughout June.  
Seeds two to five, varying in color from yellow to pink, each weighing about 25 mg [10], [11], [12], [13], [14]
Microscopic Structure 
Stem- Shows rhytidoma (outer bark) with cork consisting of 3-45 rectangular, yellow colored, thin-walled cells, arranged radially; sieve elements irregular in shape, thin-walled, a few cells containing yellowish-brown contents; phloem fibers arranged in tangential rows, consisting of 1-4 cells, each fiber short thick-walled, spindle-shaped, lignified having wide lumen; half inner portion of rhytidoma traversed by secondary phloem rays that run obliquely consisting of radially elongated parenchymatous cells having single prismatic crystals of calcium oxalate, a few cells of rhytidoma also contain prismatic crystals of calcium oxalate; stone cells also found scattered in phloem ray cells in groups, rarely single, mostly elongated, a few rounded, arranged radially, some of which contain a single prism of calcium oxalate crystals; secondary phloem, a broad zone, consisting of sieve elements and phloem fibers, traversed by multi seriate phloem rays; sieve elements arranged tangential bands and tangentially compressed cells alternating with single to five rows of phloem fibers, phloem fibers short, lignified, thick- walled having pointed ends; secondary xylem broad consisting of xylem vessels, tracheids, xylem fibers and traversed by multi seriate xylem rays; xylem vessels numerous, small to medium sized, distributed throughout xylem region in singles or in groups, groups of vessels usually arranged radially; isolated vessels cylindrical with rounded or projected at one or both ends with spiral thickening; xylem fibers numerous, lignified, large, thick-walled with wide lumen and pointed tips; xylem rays quite distinct, straight, multi seriate, consisting of radially arranged rectangular cells, each ray 30-53 cells high, 8-12 cells wide, a few ray cells containing brown contents
Powder- Yellow in color shows mostly fragments of cork cells, sieve elements, yellow colored phloem fibers entire or in pieces, stone cells in singles or in groups, numerous prismatic crystals of calcium oxalate, xylem vessels having spiral thickening, thick-walled, lignified xylem fibers and ray cells. [15]
When observed under microscope using chloral hydrate solution the powder shows following diagnostic characters—
Abundant thin-walled parenchyma, fragments of yellowish-brown cork; spherical or ovoid orange-brown granular masses
When examined under microscope using 50% v/v solution of glycerol, the powder shows simple, small and spherical to ovoid starch granules. [16]
Parts Used
Bark, root, stem, seed and fruit   
Rasaut/ Rasaanjana: Root bark and lower stem are boiled with water, stressed and condensed till a semi solid mass is obtained which is known as Rasaut. The extract called Rasaanjana is also used.   
Species approved for use as substitute for Daaruharidra (berberis aristata) are:
1. Chutro 
Taxonomic name: Berberis asiatica Roxb.
Sanskrit: Daaruharidraa, Daarvee
Malayalam: Maramanjal
Nepali: Chutro, Rasanjan
Newa: Marpyasi
Tamil: Mullukala [17], [18]
Berberis asiatica is an evergreen shrub. It grows to a height of 3.5 meter. Quite commonly found in hardy zone of UK. The plant is self fertile. Its flowers are hermaphrodite. It is pollinated by insects 
Properties: The roots contain 2.1 % berberine and stem contains 1.3%. The plant shows antibacterial, laxative, analgesic, tonic and anticancer activities. 
Medicinal uses:
Roots: used to treat fever, jaundice, ulcers, opthalmia,
Bark and stem: In Nepal bark and stem are crushed, boiled in water, strained and the liquid is evaporated till a viscous mass is obtained. It is antibacterial, laxative and tonic. It is taken internally to treat fever, and externally to treat conjunctivitis and other inflammations of the eyes.   
Tender leaf buds: They are chewed and and held against the painful tooth to treat dental caries.
The fruit: It is cooling and laxative [19]
2. Sumbal
Taxonomic name: Berberis lyceum Royle, Berberis vulgaris f. lyceum (Royle), Berberis agfhanica Schnieder, Berberis angustifolia Roxb, Berberis heteracantha Ahrendt
Of these taxonomists accepted the name: Berberis lyceum Royle  
Other Names:
Sanskrit: Daaruharidraa
English: Indian barberry, Indian lyceum, Indian lyceum, Boxthom barberry
Arabic: Ambar-baris, Ameerbarees, Zarashk
Bengali: Rasanjan, Daaruhaldi
Gujrathi: Kasmal, Rasavanti, Daaruharidraa
Hindi: Kushmul, Chutrun, Dar-chobach Mool (Root)
Kannada: Rasanjan, Mard Risin
Kashmiri: Rassashud (Root bark extract) Kaw Dach Mool (Root)
Marathi: Rasvat, Daaruhalad
Punjabi: Rassaut, Sumlu
Urdu: Sumbal, Sumblo, Ishkeen, Zark [20], [21] 
Taxonomic classification: 
Kingdom: Plantae
Unranked: Angiosperm
Unranked: Eudicots
Division: Tracheophyta
Plant Morphology: 
Berberis lyceum is a spiny, semi-deciduous, erect shrub. It is 2-4 meter tall.
Stem: terete, pale grayish, glabrous, or pubesene; internodes short, about 1.5 to 3.5 cm long, spines short, lateral spines about 0.7-1.2 cm long
Leaves: densely arranged, about 3-6 in a node; obovate, 2.7 long and 0.5-1. 5cm across, base attenuate, margin entire with 3-5 small spinules, apex acute or obtuse with tip subcoriaceous; dark green, glabrous above, paler grayish, conspicuously papillose beneath, lateral veins 3-5 on either side of the midrib, impressed above, prominently veined beneath, petiole subsessile.
Inflorescence/Flowers: racemose, 5-25 flowered, about 3-7 cm ling. Flowers bisexual, yellow, about 6-8mm across, pedicles about 6-15 mm long, prophylls ovate,  sepals in 3 series, outer series smallest and inner series largest, outer series ovate, apex obtuse, yellow, median series ovate, apex obtuse. Stamens produced at the apex. Ovary simple, oblong, ovules 4, shortly stipulate. 
Fruits: are several seeded berries, ellipsoid, glabrous, dark purple or black when ripe, 
Seeds: about 4mm long, dispersed by birds, animals, humans 
Uses: Used in Ayurvedic and Unani medicine.
Roots: To treat wounds, fractured bones, to treat piles, conjunctivitis,
Alkaloids: extracted from the plant shows anti-inflammatory, anti-oxidant and anti-microbial properties. [23]

Phytopharmacology of both the species mentioned above issame as that of Berbers aristata, hence they are approved as substitutes to Berbers aristata
Phytochemistry of Daaruharidraa (Berberis aristata) 
The main active ingredients of this plant are isoquinoline alkaloids. They are found in the root bark, stem, and berries. They are: 
Alkaloids: 
Berberine, oxyberberine, berbamine, berberrubine, aromoline, protoberberine (Karachine), taxilamine, palmatine, jatrorrhizine and oxycanthine, bervulcine, columbamine, isotetrandine and vulcracine
Other ingredients:  
Carbohydrates, organic acids like chelidonic acid, citric acid and malic acid, resin, tannin, pectin, polyphenolic compounds, some vitamins and mineral elements [24], [25]

Table 1
Phytochemistry at a glance 
Plant Species
Part of the Plant
                     Phytochemicals
Berberis
aristata
Root, Root bark 
Berberine, Oxyberberine, Berbamine, Palmatine, Aromoline, Oxycanthine. Karachine, Taxilamine, Calumbamine, Jatrorrhizine, Hydrastine and Umballiatine

Stem, Stem bark
Berberine, Oxyberberine, Berbamine, Palmatine, Aromoline and Oxycanthine

Flowers
E-Caffeic acid, Quercetin, Chlorogenic acid, Rutin and Meratin

Fruit
Citric acid and Malic acid

Heart wood
n-docosane lanost-5en-3β-ol
Berberis asiatica
Root and Stem
Berberine
Berberis lycium
Root, Stem
Berberine, Berbamine, Palmatine, Chinabine, Chinabine acetic acid, Karakoramine, Gilgitamine, Punjabine, Baluchistamine, Jhelumine, Sindamine, Ascorbic acid, Maleic acid

Identity, Purity and Strength 
Foreign matter Not more than 2 percent
Total ash Not more than 14 percent
Acid-insoluble ash Not more than 5 percent
Alcohol-soluble extractive Not less than 6 percent
Water-soluble extractive Not less than 8 percent [26] 

Tests accepted recently---- 
Foreign organic matter: Not more than 2.0 percent
Ethanol-soluble extractive: Not less than 2.0 percent
Water-soluble extractive: Not less than 6.0 percent
Total ash: Not more than 5.0 percent
Acid-insoluble ash: Not more than 1.0 percent
Heavy metals: 1.0g complies with the limit test for heavy metals
Loss on drying: Not more than 10.0 percent determined on 5.0 g by drying in oven at 1050 (scale not mentioned) [27] 
Daaruharidraa Roots contain Not less than 0.70 percent of berberine, and Stems Not less than 0.5 percent of berberine, calculated on the dried basis. [28] 

Chromosomal Identity 
Somatic chromosome numbers is 28 (n=28) in many species of Berberis including Berberis aristata. [29]

Genetic Identity 
Researchers developed DNA markers for accurate identification of Berberis aristata [30]

Properties and Pharmacology 
Ayurvedic properties
Ganas (Classical Categories)
The herb belongs to the following ganas (classical groups)
Charaka Ganas: Arshoghna (Cures Hemorrhoids), Kandughna (Anti pruritic, Respites itching), Lekhaniya (Reduces weight, Reduces fat, Relieves obesity)
Sushruta Ganas: Haridraadi, Mustaadi, Laakshaadi

Energetics:

Rasa (Taste): Kashaaya (Astringent), Tikta (Bitter)
Rasa of the Fruit: Madhura (Sweet), Amla (Sour)
Weerya (Energy State): Ushna (Hot)
Wipaaka (End result, Post Digestive Effect): Katu (Acrid, Spicy, Pungent, Piquant )
Prabhaawa (Special Effect, prominent Effect): Not specified
Gunas (Qualities): Laghu (Light), Rooksha (Dry)

Effects on Doshas: Pitta, Kapha

Actions on Dhatus: (Tissues): Meda (Adipose Tissue), Rasa (Lymph) and Rakta (Blood) 

Effects on Srotas (Systems): Annawaha (GI System), Rasawaha (Lymphatic System) 

Ayurvedic Actions:

Deepana: Appetizer
Jwaraghna: Antipyretic
Kaphaghna: Allays catarrh
Katupaushtic: Acrid, spicy, pungent tonic
Netrya: Beneficial for the eyes
Paachana: Digestive (Digestant)
Pitta saaraka: Increases the flow of bile
Rochana: Improves taste
Shothahara: Reduces swelling reduces edema
Swedajanak: Diaphoretic (Promotes sweating)
Trishna nigrhana: Reduces thirst, controls thirst, quenches thirst
Yakruduttejaka: Stimulates the functions of the liver
Warnya: Improves the complexion
Wedanaasthaapana: Anti-nociceptive (Analgesic)
Wrana shodhana: Wound cleanser, vulnerary
Wrana ropana: a wound healer [31], [32]

It is anti-inflammatory (shothaghna) and analgesic on topical application, vulnerary, antipruritic, liver stimulant, appetizer, antidiarrheal, laxative, antitussive (kaasaghna), anti-asthmatic, styptic, raktashodhana (blood purifier), rejuvenating and adaptogenic 
As it resembles in properties to those of Haridraa (Curcuma longa), Maharshi Charaka the noted Ayurvedic physician describes them together as Haridraa-dwaya (the duo of Haridraa). He makes a special mention about Daaru-Haridraa (Berberis aristata) as ‘stanya shodhana’ (one which purifies breast milk)lekhana (emaciating), arshoghna (antihemorrhoidal), kaamalaahara (allays, relieves jaundice), kandughna (anti-pruritic, allays itching), swedala (diaphoretic), rasaayana ( adaptogenic, rejuveneting) [33], [34], [35] 

Modern View
Daaruharidraa (Berberis aristata) is anti-inflammatory, anti-pyretic, analgesic, antiscorbutic, antiseptic, vulnerary, appetizer, laxative, hepatoprotectant, emmenagogue

Berberine

Molecular formula: C20H18NO4+ 
Structural formula:
In humans, oral administration of 1.2 g of berberine significantly delays small intestinal transit time. 
Eight hours after administration of 500 mg/ kg of berberine to infant rabbits, the blood concentration was 0.8 microgram/ml
Peak concentration of berberine reaches after 12 hours in the muscles and liver. [37]
Berberine is excreted through urine and feces. The elimination half-life of berberine in rats is between 5 and 6 hours, peak urinary excretion is between 12 and 24 hours while peak fecal excretion is seen after 48 hours. [38]

Pharmacology of Berberine: 

Anti-inflammatory activity:

Berberine inhibits activator protein-1activity which is essential for inflammation.
Berberine inhibits cyclo-oxygenase-2 (COX-2) enzyme.
Berberine significantly inhibits interleukin-1 (IL-1) and interleukin-8 (IL-8) and decreases leukotriene formation.
By decreasing vascular permeability, berberine inhibits inflammatory edema.

Anti-oxidant activity of Berberine:

Berberine has anti-oxidant effects in the riboflavin system. In xanthine oxidase system its anti-oxidant effect is greater than that of vitamin E. It exhibits anti-oxidant activity via inhibition of lipooxygenase and lipid peroxidation

Immunomodulating activity of Berberine:

Berberine shows significant inhibition of mitogen induced lymphocyte transformation.
Berberine inhibits neutrophil adherence and chemotaxis

Anti-microbial activity of Berberine:

Berberine has significant anti-microbial activity against Gram positive and Gram negative bacteria and fungi 

Actions on GI system of Berberine:

By delaying intestinal motility berberine shows anti-diarrheal activity. Sack et al found that berberine significantly inhibited the actions of Vibrio cholera enterotoxin and Escherichia coli enterotoxin when administered before or up to four hours after toxin injection

Actions on hepato-biliary system of Berberine: 

Berberine increases the secretion of bilirubin in rats with hyperbilirubinemia but this effect diminishes on continued administration of berberine. However a recent study shows that berberine displaces bilirubin from albumin in both in vitro and animal studies, resulting in an increase in serum total and direct bilirubin concentrations. In an in vitro study, berberine has been shown to be hepatoprotective when administered twice a day for two days before receiving toxic doses of paracetamol

Summary: 

To admire pleiotropic pharmacological activity of Daaruharidraa (Berberis aristata) and an alkaloid berberine found in the plant, a doyen reverse pharmacologist ADB Vaidya writes:
" The multiple uses and actions of the plant, Berberis aristata (Daruharidra), have always intrigued pharmacologists and clinicians. It is a topical antimicrobial par excellence in ayurveda. Its use, as extract for eye drops in conjunctivitis, is wide spread. The active principle of the plant, berberine, has been extensively studied. the activity of berberine against a variety of organisms, including bacteria, viruses, fungi, protozoa, helminths and chlamydia, has been demonstrated. Berberine has been shown to bind to DNA and inhibit cleavage. There is an urgent need to develop specially targeted drug delivery systems of berberine, for topical and systemic antimicrobial use. Local anesthetic, pigment inducing, enzyme inhibitory, anti-hypertensive, anti-pruritic and anti-pyretic activities have been reported with berberine. Recently, the antiamnesic activity of berberine has been reported. Despite the diversity of activities, the proper clinical clinical documentation of the reverse pharmacology of the plant has been neglected. Its beneficial effects on Plasmodium vivax relapses have been reported by Gogte. But experimental documentation is urgently needed. [39]         
Phytopharmacology of berberine is also described in detail in the chapter on Guduchee (Tinospora cordifolia)

Oxyberberine  

Molecular formula: C20H17NO5
Structural formula:

Pharmacology of oxyberberine is similar to that of berberine [40], [41]


Berbamine    

Molecular formula: C37H40N2O5
Structural formula:

Berbamine is calcium channel blocker. [42] 

Berberrubine (Hydrochloride)

Molecular formula: C19H16NO4
Structural formula: 
     [43]

Pharmacology of berberrubine hydrochloride is similar to that of berberine, but berberrubine hydrochloride has predominantly anti-tumor activity. [44]

Aromoline

Molecular formula: C36H38N2O6
Structural formula:
                         [45]

Pharmacology of aromoline is similar to berberine. In addition it shows vasodilator, anti-hihtaminic, anti-amoebic and anti-plasmodial activity. [46]

Protoberberine (Karachine)

Molecular formula: C26H27NO5   [47]
Structural formula: 
                           [48]

Berberine, Protoberberine and Palmatine belong to isoquinoline alkaloids. 
The protoberberine alkaloids display a broad range of pharmacological activities as mentioned in folk medicine in China, India and many other Asian countries.
They inhibit acetylcholine esterase comparable to physostigmine. [49]
The Protoberberine alkaloids (Berberine Palmatine, Jatrorrhizineexhibit antimalarial activity. [50]

Palmatine 

Molecular formula: C21H24NO4+
Structural formula:

Palmatine is a protoberberine alkaloid found in many plants. This has been used to treat inflammations, hypertension, dysentery, jaundice and liver diseases.
This compound has a potential for the treatment of flavivirus infection. [51], [52]

Jatrorrhizine 

Molecular formula: C20H20NO4
Structural formula:
Jatrorrhizine is a protoberberine alkaloid found in many plants. It shows anti-inflammatory, antibacterial, antiviral, antifungal and anti-parasitic activity. In large doses (50-100 mg/kg), in rats it reduces blood sugar. It improves blood flow in chemically poisoned rat liver. It interferes with MDR cancer cells. Its synthetic derivative has stronger antibacterial activity. [53]

Chelidonic acid  

Molecular formula: C7H4O6
Structural formula:

Chelidonic acid exhibits anti allergic activity. It decreases Ig E levels, decreases eosinophils and mast cells in the nasal mucosa in allergic rhinitis.  [54], [55] 

Table 2

Phytopharmacology of Daaruharidraa (Berberis aristataat a glance 

Action
Preparations           and
Dosages
         Experimental Evidence
Anti-inflammatory
Aqueous extract of Root, 500 to 1000mg/kg
Carrageenan induced paw edema in rats.
Significant reduction in paw edema.

Hydro-alcoholic extract of Root,
50 mg to 100 mg/kg
Carrageenan induced paw edema in rats.
Significant reduction in paw edema.

Aqueous extract of the plant
150 to 200 µg/l
Endotoxin induced uveitis in rabbits.
Significant improvement of chronic uveitis
Anti-oxidant
Ethanolic extract of Root bark; 500mg to 1500mg/kg

Acidified Chloroform-methanol fraction
100 to 125mg/kg

Basified Chloroform-methanol fraction
4 to- 5 mg/kg
Alloxan induced diabetes in female rabbits.
Improvement in diabetes, restoration of anti-oxidant status as evidenced by improvement in biochemical markers.
Immunomodulatory
Isolated berberine
On mice: Improved immune response, altered the cource of infectious diseases and airway inflammations
Clinical study in humans: Improvement in allergies and bronchial asthma.
Antipyretic
Aqueous and alcoholic extract of Root 200mg/kg
On Rabbits: Lowered significantly rectal temperature
Adaptogenic
Aqueous/Alcoholic extract of Root 250mg/kg
Rats: Increase in bodyweight
On the Skin
Standardised extract
Clinical study: Inhibition of Tyrosinase, reduction in hyperpigmentation, lightnening of skin color
On Hematopoetic system
Alcoholic extract of Root
On animal model: Anti-platelet activating factor
Anti-arthritic
Hydroalcoholic extract of of Root/Stem/Plant
50-100-200 mg/kg
 Animal model: Significant reduction in joint swelling and inflammation as evidenced by regression in inflammatory markers and on histological study
Antiosteoporotic
Aqueous-Methanolic extract of Root/Stem/Plant
100-200-300mg/kg
 Oophorectomized Rats: Significant reduction in osteoclastic activity, increase in osteoblastic activity, increase in bone density
On Eye
Isolated Berberine
Eye drops
Clinical trials on conjunctivitis:
Complete remission from conjunctivitis
On Breast
Methanolic Extracts of various parts of the plant; 125-250-500 µg/ml
Cancer cell line; apoptosis of MCF-7 cells.
Anti-Microbial




 Antiparasitic 
Leaf and Root extract




Isolated Berberine extract, 5mg/ml
Inhibition of the growth of Staphylococcus aureus, proteus mirabilis, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter species and Candida albicans, Aspergillus flavus, Aspergillus fumigantes, Mucor and many Gram positive and negative fungi

Inhibition of nuclear DNA of Leishmania donovani
Analgesic
Aqueous and alcoholic extract of Root 50 to 100g
On Albino rats: Significant increase in reaction time.
Sedative/Anxiolytic/Antistress/Hypnosis
Aqueous extract of Root; 5-10-20mg/kg
On Mice; Intraperitoneal injection. Significant motor inco-ordination and prolonged hypnosis
Neuroprotection
Root extract in suitable solvants
Animal models. Protection against global ischemia, and Parkinsonism, Alzheimer’s Disease
Anti-depressant
Isolated Berberibe, 5-10-20mg /ks

On Mice; Inhibition of immobility period, reversal of reserpine-induced behavioral despair, enhancement of the anti-immobility effect
On CVS
Fruit;
Berberis sulphate solution; 5mg/ml
Animal model: Selective inotropic action
Dogs, Cats, Rats and Frogs: Antihypertensive: Redustion of systolic blood pressure and producing bradycardia  
On RS
Extracts of the plant
Clinical study on patients of chronic pharyngitis; Relief from symptoms
Antidiarrheal





Antiamoebic

Isolated Berberine

Ethylalcohol extract of stem 250mg to 500mg/kg

Isolated Berberine
100mg in Mice

150mg in Hamsters

Rabbit: core of E.coli-induced and castor oil induced diarrhea
Wistar albino rats: Increased intestinal absorption of water by decreasing intestinal motility


In Mice, In Hamsters: Cure of acute dysentery and prevention of amoebic hepatitis
Hepatoprotection
Aqueous methanol extract of Fruit
500mg/kg
Swiss male albino mice and male albino Wistar Rats: Protection against paracetamol-induced and CCl4-induced  hepatotoxicity
Antidiabetic
Ethanolic extract of Root bark, 0.5 to 1.5 G/kg

Ethanolic extract of Root; 250mg/kg
Alloxan-induced female albino Rabbits. Stimulation of release of insulin and exhibition of insulin like action

Alloxan-induced male Wistar albino Rats: Lowers bloo glucose levels
Antineoplastic
Aqueous and Alcoholic extract,
3289µg/ml
Ehrlich Ascites Carcinoma induced in albino mice. Decrease in cancer cell number and increase in life span


Some Testimonials from Modern Research:

General Pharmacology

Berberine is a bioactive ingredient found in Daaruharidraa (Berberis aristata). It is rapidly absorbed. Its concentration in the blood depends upon the dose administered. It is metabolized in the liver with phase I demethylation and phase II glucuronidation. The phase I metabolism of berberine is partially reduced by SKF-525A treatment, but the phase II glucuronidation of berberine is not affected by probenecid. [56]

Adaptogenic Activity 


In a study on animal model (rats) oral administration of 250mg/kg bodyweight of the extract of root of Daaruharidraa (Berberis aristata) for 14 days marginally improved the body weight of the animals where as administration for 21 days increased the body weight of the animals by 11.27% [57]

Anti-Inflammatory Activity 


To evaluate anti-inflammatory and anti-granuloma activity of hydroalcoholic extract of Daaruharidraa (Berberine aristata); carrageenan, cotton pellets were used to induce paw edema and granuloma complete Freund’s adjuvant to induce stimulation of peritoneal macrophages in rats. Serum levels of inflammatory markers were assessed. Expression of peritoneal macrophages to derive the plausible mechanism of hydroalcoholic extract of Daaruharidraa (Berberine aristata) in activated peritoneal macrophages. Pretreatment with the extract showed significant reduction in paw edema granuloma. The treatment also showed significant reduction in serum levels of inflammatory markers. Protein expression of pro-inflammatory markers was found to be reduced in stimulated macorphages.  [58]

Antioxidant Activity 


Due to oxidative stress activities of superoxide dismutase, catalase, glutathione peroxidase and reductase are decreased. By administration of the extract of root of Daaruharidraa (Berberis aristata) these activities are increased. The extract of root of Daaruharidraa (Berberis aristata) has a strong potential to reduce oxidative stress. [59] 

Immunomodulatory activity 

Interleukin (IL)-12 plays a pivotal role in the development of T helper type 1 (Th1)-immune response, which may have therapeutic effects on diseases associated with pathologic Th2 responses such allergic disorder and bronchial asthma. In an experimental study on mice berberine a key phytochemical found in Daaruharidraa (Berberis aristata) was found to be a potent immunomodulator. When used as an immunotherapeutic agent, it altered the course of infectious diseases and airway inflammation. [60]

Actions on the Skin 


Tyrosinase is copper containing enzyme controlling the production of melanin. It is present in animal and plant tissues. It catalyses the production of melanin and other pigments from tyrosine. Traditionally the stem-bark and wood of Daaruharidra (Berberis aristata) was used to lighten the skin color and as an exfoliating scrub in India. The standardized extract of Daaruharidra (Berberis aristata) was found to possess anti-tyrosinase activity. Various solvents were used to extract bioactive phytochemicals from the plant. Of these, methanol extract showed maximum tyrosinase inhibition. This shows that methanol extract of the plant has anti-hyperpigmentation potential on human skin. In my opinion Daaruharidra (Berberis aristata) can be used in cosmetic preparations to lighten the skin color. [61], [62]

Berberine the key phytochemical isolated from Daaruharidraa (Berberis aristata) showed cytotoxic activity against melanoma. The melanoma B16 cells were much more sensitive to berberine than the U937 cells. [63]

Wound healing 


The pharmacological actions of Berberis asiatica and Berberis lyceum are same as those of Berberis aristata. They are therefore approved substitutes where Berberis aristata is unavailable. The aqueous and methanolic extracts of the root of Berberis lyceumhave been examined for their wound healing potential. In experimental studies on Swiss Wistar rats, incised and excised wounds were created. Both the extracts increased the area of epithelization. In wounds treated with aqueous extracts, moderate collagen deposition, fibroblasts and macrophages were found; whereas in wounds treated with methanol extracts, a significant increase in collagen deposition with lesser fibroblasts and macrophages were observed. This shows that the methanol extract was more effective than the aqueous extract.  [64]
Crude extract of root of Daaruharidraa (Berberis aristata) known as “Rasaut” and the extract of the bark mixed with honey is useful application to treat skin ulcers. [65]

Antimicrobial Activity/ Antibacterial activity 

The hydroalcoholic extract of Berberis aristata exhibits antibacterial activity against Micrococcus leuteus, Bacillus subtilis, Berberis cereus, Enterobactor aerogenus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, and Streptococcus pneumonia.   
Berberine isolated from Daaruhadriraa (Berberis aristata) displayed antibacterial effect on multidrug resistant Escherichia coli. The effect is dependant on the dose of berberine. Berberine exerts antibacterial activity by binding tightly to the DNA of the organism. [66]

Antiviral activity 

A study showed that berberine chloride inhibited the replication of human cytomegalo virus (HCMV). The activity was similar to that of gancyclovir. The mechanism of inhibition of HCMV by berberine was presumed to be different from that by gancyclovir. It is said that berberine interfered with intracellular events taking place in the cell after virus penetrated the host cell but before viral DNA synthesis. [67]  
In another study on antiviral activity of the ethanol extract of Daaruhadriraa (Berberis aristata) containing the alkaloidberberine, showed strong inhibition of the growth of of H1N1 influenza ‘A’ strains PR/8/34 or WS/33 in RAW 264.7 macrophage-cells, A549 human lung epithelium-derived cells and murine bonemarrow derived macrophages but not MDCK canine kidney cells. [68]

Antifungal activity 

In one study berberine a key phytochemical found in Daaruharidraa (Berberis aristata) at concentrations of 100 to 1000 ppm significantly inhibited spore germination of many fungi. The best antifungal activity was observed at a concentration level of 800 ppm.
In another study, at concentrations 10-25 mg/ml inhibited the growth of Alternaria, Aspergillus flavus, Aspergillus fumigantus, Candida albicans,  Curvularia, Drechslera, Fusarium, Mucor, Penicillium, Rhizopus oryzae. At a concentration of 50mg/ml it inhibited the growth of Syncephalastrum aussi, Aspergillus niger.[69], [70]
The hydroalcoholic extract of Daaruharidraa (Berberis aristata) exhibits anti-fungal activity against Aspergillus nidulans, Candida albicans, Aspergillus terreus, Trichophyton rubrum, Aspergillus spinulous, Cryptococcus albidus, Aspergillus flavusand Aspergillus niger. [71] 

Antimalarial activity 


The root bark of Daaruharidraa (Berberis aristata) exerts a significant schizont inhibition of Plasmodium berghei. Aqueous extract of Daaruharidraa (Berberis aristata) also known as Indian Barberry shows antimalarial activity in animal models. [72], [73] :italic'>berberine, showed strong inhibition of the growth of of H1N1 influenza ‘A’ strains PR/8/34 or WS/33 in RAW 264.7 macrophage-cells, A549 human lung epithelium-derived cells and murine bonemarrow derived macrophages but not MDCK canine kidney cells. [68]
(Also see above: Ref. 39)

Actions on RES/ Hematopoietic System 

In Ayurvedic system of medicine, Daaruharidraa (berberis aristata) is in use for the management of various allergic disorders. In an experimental study the alcoholic extract of the root of Daaruharidraa (berberis aristata) is shown to exhibit anti-platelet activating factor (PAF) activity. The extract has been shown to inhibit PAF induced platelet aggregation on rabbit platelets. The alcoholic extract of the root of Daaruharidraa (berberis aristata) also inhibited [3H] labeled PAF binding to rabbit platelets in a competitive manner, [74]
Berberine is the key alkaloid found in Daaruharidraa (berberis aristata). Of many phytochemicals berberine exerts almost all pharmacological actions of Daaruharidraa (berberis aristata). Berberine exhibited the ability to iduce apoptosis in promyelocytic leukemia HL-60 cells. After 48 hours, the cells treated with berberine at concentration of 25µg/ml underwent cell cycle arrest while palmatine a berberine analog was not able to induce apoptosis. From this observation, the researchers feel some important cellular process other than the intracellular DNA-interacting action of of berberine may be involved in the berberine-induced apoptosis in HL-60 cells. [75]
Berberine induces significant changes in mitochondrial membrane potential in human promonocytic U937 cells. Activation of caspase-9 and caspase-3 is the mechanism through which berberine induces apoptosis of U937 cells. [76]
Berberine produces apoptosis through mitochondrial/caspase pathway in human promonocytic U937 cells. [77]

Antiparasitic Activity 

Berberine is the key alkaloid found in Daaruharidraa (berberis aristata). In an experimental study hamsters infected with Leishmania donovani were treated with Daaruharidraa (berberis aristata) for eight days and for a long term. The result showed that the parasitic load reduced. Therefore some researchers feel that berberine an alkaloid isolated from Daaruharidraa (berberis aristata) may be useful for the treatment of visceral leishmaniasis. [78]
In an experimental study on hamsters, berberine an alkaloid isolated from Daaruharidraa (berberis aristata) was shown to prevent the development of amoebic liver abscess. [79] 

Actions on Musculoskeletal System 

To evaluate anti-arthritic activity of hydroalcoholic extract of Daaruharidra (Berberis aristata) arthritis was induced by subplantar injection of 2% (v/v) formaldehyde. The     arthritis was treated by using the extract at doses of 50, 100 and 200 mg/kg orally. The inflammation decreased significantly as evidenced by decrease in joint diameter and reduced inflammatory cell infiltration in histopathological study. Further the beneficial effect of the extract was substantiated with decreased expression of inflammatory markers, IL-1β, IL6, TNF-R-1 and VEGF by immunohistochemistry analysis. [80]
A study was undertaken to evaluate anti-osteoporotic effect of Daaruharidraa (Berberis aristata) in oophorectomized rats. The oophorectomized animals were treated with 100, 300 and 500 mg/kg bodyweight of aqueous-methanol extract of Daaruharidraa (Berberis aristata) for 42 days. The results showed anti-osteoporotic activity of the extract of Daaruharidraa (Berberis aristata) [81]
Berberine is the key phytochemical found in Daaruharidraa (Berberis aristata). It inhibits osteoclast formation. It helps survival of osteoclasts through suppressing the NFκ-B and Akt pathways, thus prevents bone destruction. [82]
Villoo Morawala Pattell treated osteoporosis successfully with the extract of Daaruharidraa (Berberis aristata) and obtained patent for extraction process of active phytochemical (patent No. WO 2008007215 A2) [83] 

Actions on the Breast 


In a study the methanolic extract of Daaruharidraa (Berberis aristata) was used to treat human breast cancer line MCF-7. The different concentrations of the methanolic extract used were: 125, 250 and 500µg/mL. The significant response of apoptosis of cancer cells was seen at the concentration of 500µg/mL. [84] 

Actions on Nervous System

Three doses (5, 10, 20 mg/kg bodyweight) of the root extract of Daaruharidraa (Berberis aristata) were injected intra peritoneally in mice in comparison with 3mg/kg bodyweight of diazepam as positive control. After 30 minutes of injection of extract (40mg/kg bodyweight) thiopentone sodium was injected and increase in sleeping time by extract was recorded. The result showed that the dose of 5mg/kg did not affect the locomotor activity where as the dose of 20mg/kg significantly reduced the motility. There was significant motor incoordination and prolonged hypnosis as compared to diazepam. [85]

The root extract of Daaruharidraa (Berberis aristata) shows neuroprotective effect against global ischemia, ischemia reperfusion injury and 6-OHDA induced Parkinson’s disease [86] 

When studied on albino rats and mice, at 50, 100 1nd 200mg/kg doses Daaruharidraa (Berberis aristata) showed marked analgesic activity. [87]

Berberine is the key alkaloid found in Daaruharidraa (berberis aristata). Evidences from modern research demonstrated that in humans Daaruharidraa (Berberis aristata) exerts important pharmacological actions. It inhibits monoamino oxidase-A (MAO-A), an enzyme involved in the degradation of norepinephrine and serotonin. In an experimental study on mice berberine at 5, 10 and 20 mg/kg bodyweight exhibited antidepressant activity. It also reversed reserpine-induced behavioral despair. At lower doses, berberine did not affect the locomotor activity and barbiturate-induced sleep time. It produced mild hypothermic action in rats and displayed analgesic effect in mice. [88] 

In another study berberine isolated from the species ‘Berberis’ showed anticonvulsant activity. Some researchers therefore feel species of ‘Berberis’ berberine to be precise may be used for the treatment of convulsions and epilepsy. [89]

Actions on the eye

Lipopolysaccharide (LPS), a glycolipid derived from the outer cell membranes of Gram-negative bacteria is a pro-inflammatory agent. Administered by a systemic or ocular route LPS induces uveitis. A study was undertaken to investigate anti-inflammatory activity of aqueous extract of Daaruharidraa (Berberis aristata) in LPS induced uveitis in rabbits. Anterior uveitis was induced in rabbits by intravitreal injection of LPS from Escherichia coli. Topical instillation of aqueous extract of Daaruharidraa (Berberis aristata) showed potent anti-inflammatory activity against endotoxin induced uveitis. [90]

Daaruharidraa (Berberis aristata) is documented to exhibit anti-inflammatory and anti-histaminic effects. The Unani eye drop is a polyherbal formulation containing Daaruharidraa (Berberis aristata) as a key ingredient. The Unani eye drop formulation exhibited significant anti-inflammatory and antihistaminic effect in turpentine liniment induced ocular inflammation in rabbits. [91], [92]

Actions on CVS

Daaruharidraa (Berberis aristata) an edible plant is employed as medicine in South Asia. In particular, the fruit of the plant is used as a tonic for liver and heart. In isolated heart tissue, the extract of the fruit of Daaruharidraa (Berberis aristata) exhibits a positive inotropic action. After several studies the researchers believe, Daaruharidraa (Berberis aristata) contains active principles that cause a selective inotropic effect involving the modulatory effect on actin myosin cooperativity. Further studies may lead to isolation of new cardiotonic agents from the fruit of Daaruharidraa (Berberis aristata). [93]
Pharmacological actions of Berberis vulgaris are similar. In rats hypertension was induced by administering deoxycorticosterone acetate (DOCA). The aqueous extract of Berberis vulgaris fruit was tested to evaluate antihypertensive effect. The results suggested that the Berberis vulgaris fruit have vasodilatory effect and lowered elevated blood pressure in rats. It is said that the antihypertensive and vasodilatory effects of the fruit were endothelium-independent and may be used to treat hypertension with endothelial dysfunction. [94], [95] 

Actions on RS 

In a study, 120 patients of chronic pharyngitis were treated with the etract of Daaruharidraa (Berberis aristata). In 60 patients the extract was administered systemically and in 60 patients oral rinse was recommended. The results showed that the outcome of trial was superior for systemic usage than oral rinse. [96]

Actions on GI System 

Crude extract of root of Daaruharidraa (Berberis aristata) known as “Rasaut” shows antiulcer activity. The phytochemical that exerts this action is berberine. [97] 
The ethanol extract of the bark of Daaruharidraa (Berberis aristata) shows a potent antidiarrhal activity. The extract shows antibacterial activity against all strains of Shiegella. [98] 
In experimental study on rats the alcoholic extract of the stem of Daaruharidraa (Berberis aristata) was shown to prevent intestinal fluid accumulation. This is the mechanism of antidiarrheal activity of Daaruharidraa (Berberis aristata). [99]
The aqueous extract of barberry fruit showed antihistaminic and antocholinergic activity. [100]
The methanolic extract of the stem of Daaruharidraa (Berberis aristata) showed anti cancer potential against human colon cancer cell line HT 29 [101]

Actions on the Liver 

(A). Hepatoprotection 

Pre-treatment of mice with aqueous extract of fruit (500mg/kg) and plant extract of Daaruharidraa (Berberis aristata) (500mg/kg) protected the animals from paracetamol and carbontetrachloride (CCL4)-induced hepatotoxicity [102]

In another study, to evaluate the hepatoprotective activity of Daaruharidraa (Berberis aristata) against carbontetrachloride hepatotoxicity, ethanolic extract of Daaruharidraa (Berberis aristata) was administered orally to albino Wistar rats weighing 150-200gms of either sex, in the dose of 400mg/kg/day for 7 days.  The treatment significantly lowered the elevated levels of SGOT, SGPT, alkaline phosphatase and bilirubin in the animals with carbontetrachloride-induced hepatotoxicity. The histological examination of the liver demonstrated preservation of hepatic architecture, reduction in necrosis and inflammatory cell infiltration. This confirmed the hepatoprotective effect of Daaruharidraa (Berberis aristata) against carbontetrachloride-induced hepatotoxicity. [103], [104]

(B). Infective Hepatitis 

A polyherbal formulation containing Daaruharidraa (Berberis aristata) as a key hepatoprotectant prevented the development of amoebic liver abscess in golden hamsters. [105]

(C). Fatty Liver Disease/Hepatic Fibrosis 

Extracts of Daaruharidraa (Berberis aristata) reduce liver fibrosis by protecting hepatocytes from apoptosis. The extract inhibits the liberation of hepatocyte-derived apoptotic bodies and DAMPs and some initial profibrogenic stimuli. This effect is mediated through mitochondrial pathway. [106]
Dimethylnitrosamine (DMN) is a potent hepatotoxin. It can cause fibrosis of the liver. To evaluate the efficacy of Daaruharidraa (Berberis aristata) to prevent, arrest or to treat (?cure) the cirrhosis induced by DMN, cirrhosis was induced in rats by intraperitoneal injection of DMN. The animals were then treated with aqueous and ethanolic extract of Daaruharidraa (Berberis aristata). The effects were assessed by biochemical markers and histological studies. Both the extracts at 200mg/kg bodyweight showed significant anti-cirrhosis activity, similar to that of silymarine. However researchers feel that ethanolic extract was more effective than aqueous extract [107]

Actions on metabolism 

The extract of Daaruharidraa (Berberis aristata) decreases hepatic glycogen content restores to normal levels. [108] 
A study was undertaken to evaluate the effect of Daaruharidraa (Berberis aristata) on lipid profile and coagulation parameters after feeding healthy rabbits of either sex on high cholesterol diet for 45 days. The animals treated with Daaruharidraa (Berberis aristata)
(25mg/kg bodyweight) showed a significant reduction in serum cholesterol, triglycerides and low density lipoprotein levels after 30 days; more over, there was an increase in thrombin time (TT, thrombin clotting time TCT). [109] 

A study was undertaken to evaluate the efficacy of a combination of Daaruharidraa (Berberis aristata) and Sylibum marianum extrat (BerberolR) in overweight, dyslipidemic 105 Caucasian patients. They were advised to take one tablet at lunch and one tablen at dinner for six months. The results showed that the body weight and body mass index of the patients reduced, insulin resistance decreased, levels of fasting plasma glucose, fasting insulin,  total cholesterol, LDL-C, triglycerides, retinol binding protein-4 (RBP-4), adeponectin, and Homoeostatic Model Assessment (HOMA-IR) decreased. (HOMA-IR is a method for assessing β-cell function and insulin resistance from fasting glucose and insulin or C-peptide concentration) while the level of HDL-C increased [110] Interestingly the combination Daaruharidraa (Berberis aristata) and Sylibum marianum extrat (BerberolR) is useful to treat dyslipidemia in patients that do not tolerate high doses of statins. [111]

The mechanism of lipid lowering activity of Berberine from extracted from plants and plant stanols on Syrian hamsters. The hamsters were treated with 0.17% berberine equivalent to 100mg/kg bodyweight or with 1% plant stanol; and a thrd group with a combination of berberine and plant stanol 1% for 4 weeks. In all the groups the elevated lipid levels were lowered significantly. Plasma lipids were analyzed with enzymatic methods, cholesterol absorption and synthesis by using stable isotope tracer methodology and gene and protein expressions in the liver and small intestine using real-time PCR and Western blot respectively. The findings of the study suggest that cholesterol-lowering action ob berberine might involve a combination of cholesterol absorption and stimulation of bile acid synthesis. [112] 

Antidiabetic activity 

To evaluate the efficacy of Daaruharidraa (Berberis aristata) on diabetic rats, by administering streptozotocin, diabetes was induced in adult male Wistar rats. The methanolic extract of the stem of Daaruharidraa (Berberis aristata) was then administered at doses of 250mg/kg and 500mg/kg bodyweight. The treatment controlled the diabetes very well. The treatment also lowered the levels of elevated lipids and elevated the level of high density lipoprotein (HDL) [113]
Similar results are reported by researchers using the extract of the root and stem bark of Daaruharidraa (Berberis aristata) in alloxan-induced diabetic rats. Some researchers combined Daaruharidraa (Berberis aristata) with Silybum marianum. [114], [115], [116]

Hydroalcoholic extract of Daaruharidraa (Berberis ariststa) is useful for prevention and treatment of neuro-vascular complications of type 2 diabetes. [117] 
Inspite of conventional treatment in some patients, diabetes mellitus remains uncontrolled. Sixty patients of type 2 diabetes with varying severity were selected for treatment with berberine isolated from Daaruharidraa (Berberis aristata). For them oral doses ranging from 0.3 to 0.5 g three times a day were prescribed for 1 to 3 months together with a therapeutic diet for 1 month. Sixty percent of the patients showed fasting glycemic control. It is suggested that berberine promotes functional recovery of β-cells. [118] 

Berberine stimulates glucose transport through a mechanism distinct from insulin. 

Berberine is known as 5’ adenosine monophosphate-activated protein kinase activator. Its hypoglycemic effect is independent to insulin. Its hypoglycemic effect is related to inhibition of mitochondrial function, stimulation of glycolysis and activation of AMPKinase pathway. Additionally, berberine may also act as an α-glucosidase inhibitor. In the newly diagnosed type 2 diabetics, berberine is able to lower blood insulin level via enhancing insulin sensitivity. In patients with poor β-cell function, berberine may improve insulin secretion via resuscitating exhausted islet cells. Furthermore, berberine may have extra beneficial effects in preventing cardiovascular complications due to its lipid lowering, antiarrhythmic and nitric oxide inducing properties. Additionally antioxidant property of berberine may be useful in preventing and alleviating diabetic nephropathy. [119], [120]

Actions on Male Reproductive System 

Berberine a key phytochemical found in Daaruharidraa (Berberis aristata) markedly inhibits the proliferation of prostate cancer. The inhibitory effect depends upon the concentration of the extract and the dose administered. [121]

Actions on Female Reproductive System 

Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of Polycystic Ovary Disease (PCOD) / Polycystic Ovary Syndrome (PCOS). The condition is characterized by presence of polysystic ovaries on pelvic scanning, ovulatory dysfunction and hyperandrogenism. Insulin resistance is a significant long term risk factor for cardiovascular disease and complications of metabolic syndrome. Berberine, a plant alkaloid from ‘Berberis’ species reduces insulin resistance and facilitates ovulation induction in women with PCOS or PCOD. In a clinical trial, women taking berberine orally for 12 weeks became euglycemic and started ovulation. [122], [123]
Many menopausal women develop dyslipidemia and vasomotor symptoms. Berberine from plant species not only prevents but controls and cures these symptoms. [124] 

Antitumor activity

Berberine is an alkaloid isolated from Daaruharidraa (Berberis aristata). In fact all pharmacological actions of Daaruharidraa (Berberis aristata) are exerted via berberine. Methylcholanthrene and 20-methylcholanthrene are highly carcinogenic polycyclic aromatic hydrocarbons. Of the two, 20-methylcholanthrene is more carcinogenic. To evaluate the anticancer activity of Daaruharidraa (Berberis aristata), 200/ 0.1 mL was administered to mouse 5 days a week for 20 weeks. Administration of berberine at 0.5, 2.5, or 5mg/kg bodyweight significantly reduced the incidence of tumor and increased the lifespan in rats. [125] 
A study shows Ehrlich ascites carcinoma (EAC) cell line was sensitive to non-photoactivated berberine than NIH-3T3 (3-day transfer inoculums 3x105) cell line. UVA irradiation increased the sensitivity of EAC cells to berberine while the sensitivity of NIH-3T3 cells to photoactivated berberine was not changed. Berberine significantly induced direct DNA strand breaks in tested cells. The DNA damage generated by the combination of berberine with UVA irradiation induced a significant blockage of EAC cells in S and G2/M phases.  [126] 
The aqueous extract (100mg/kg) and ethanol extract 6.5mg/kg) of Daaruharidra (Berberis aristata) showed anticancer activity against Ehrlich ascites carcinoma in mice. Of the two, the ethanol extract was superior in action. A study showed that their action was not as potent as cisplatin. However the combination of cisplatin and the extracts of Daaruharidra (Berberis aristata) showed more efficient anticancer activity against Ehrlich ascites carcinoma bearing mice. [127] 
The combination of mitomycin C and cisplatin is beneficial in the treatment of various cancers. However the treatment culminates into mitochondrial dysfunction. Administration of Daaruharidraa (Berberis aristata) at the dose of 10mg/kg body weight shows protective effects on mitochondrial dysfunction caused by mitomycin C and cisplatin. [128] 
Till date researchers had focused their research to study anticancer activity of individual phytpchemical from various plants. For the first time some researchers studied the anticancer activity of a combination of Berberine from Daaruharidraa (Berberis aristata) and Curcumin from Haridraa-Turmeric (Curcuma longa) against some cancers. They showed that the anticancer activity of the combination was much superior to individual or single phytochemical. Here are their results against some cancers such as: 

Anticancer activity against 549 cells, Against Hep G-2 Cells, Against MCF-7 Cells, Against Jurkat Cells, Against K562 Cells etc.

Berberine (at a concentration of 0.5mg/mL) and Curcumin (at a concentration of 1.25mg/mL) were found to have inhibitory activity of 64% and 60% respectively. The combination of Berberine and Curcumin in 1:1 ratio brought about 99% inhibition [129] 

Culinary Uses

The fruits are eaten as dessert. They are succulent, sweet and contain nutrients and antioxidants. The roots and fruits are used to prepare alcoholic drinks. The acidic flower buds are made into sauce. 

Medicinal Actions and Uses 

Traditional Uses

Daaruharidraa (B. aristata) is used externally to treat skin inflammations, contusions, wounds and ulcers. To treat conjunctivitis, trachoma and ophthalmic conditions “Rasaanjana” is used. 
Internally it is used to treat PUO, malaria, to quench excessive thirst, to improve appetite, to treat diarrhea, jaundice, to eliminate poisons and toxins, for bronchitis, bronchial asthma, for urinary problems, menstrual problems, to treat gynecological problems etc.
Daaruharidraa (Berberis aristata) has been in use worldwide for the treatment of diarrhea, diseases of the liver and gallbladder. It is used as a bitter tonic, stomachic, cholagogue, antiperiodic and alterative in cases of remittent and intermittent fevers
In India, its preparation ‘Rasaut’ mixed with honey is used for mukhapaaka (stomatitis, aphthous ulcers), abrasions and ulcerations of the skin.  [130] 

Ayurvedic Usages 

Internal-It is indicated for liver disorders, arsha (bleeding hemorrhoids), paandu (anemia), kaamalaa (jaundice), agnimaandya (loss of appetite), aruchi (loss of taste), rakta pitta, rakta pradara (menorrhegia), shweta pradara (leucorrhea), kushtha (leprosy), kandu (itching), jwara (PUO).

External- Netra vikaara (ophthalmic disorders especially inflammatory or infective such as conjunctivitis), karna shoola (ottalgia), pooti karna (purulent discharge from the ear), gandamaalaa (cervical lymphadenitis mostly tubercular), bhagandara (fistula), mukharoga (stomatitis) 
Darwyaadi Ghana Sattwa watee has been used in Shwetapradara (Leucorrhea) and other diseases. 
Ayurvedic practitioners use it to treat jaundice, enlargement of liver and spleen (portal hypertension).  [131]

Usages in Modern Medicine 

Daaruharidraa (Berberis aristata) contains berberine. It can therefore be used to treat all the ailments where berberine is used. Pharmacological actions and medicinal usages of berberine have been discussed in detail in the chapter on Guduchee (Tinospora cordifolia

Here are some more usages

1. Stomatitis, glossitis, gingivitis, dyspepsia, hyperacidity, diarrhea,   IBD, helminthiasis
2. Viral hepatitis
3. Dermatitis, psoriasis
4. Vaginitis, leucorrhea
5. Toxic shock syndrome
6. Pharyngitis, bronchitis
7. Dyslipidemia.
8. Diabetes      [132]

Toxicity 

LD50 value of berberine in mice was found to be 25.3 mg/kg I. P. But in human beings berberine is free from any serious toxicity.
In larger doses Daaruharidraa (Berberis aristata) can be toxic giving rise to symptoms such as vomiting, severe diarrhea, excessive sweating, lethargy, nose bleed, severe hypotension, skin and eye irritation and urinary problems. In such cases the drug or any preparations containing   Daaruharidraa (Berberis aristata) should be withdrawn. 
Standardized extracts of the plant can cause stomach upset and should not be used for more than two weeks at a time

Contraindications

It is contraindicated for infants and young children. In pregnant women it can cause uterine contractions and in first trimester can cause abortion. It is contraindicated during lactation.
It is toxic to growing sperm cells. Hence males of reproductive age group should not use it as it may contribute to sterility 

Drug Interactions

It interacts with doxycycline, tetracycline. Interactions with other antibiotics should also be borne in mind. 

Preparations and Dosages 

Any form of the preparation should not be taken for more than five days at a time 

Decoction: To make decoction, take a teaspoon of bark, and 100 to 150 ml of water, bring to boiling, leave for 10 to 15 minutes.
Dose: 50 to 100 mL

Decoction of the Stem: 5 to 15 mL.

Extracts: Standardized to contain 5 to 10% alkaloids, with a total of approximately 500 mg of berberine is the recommended dosage; 1-3 g (CCRAS); extract of dried stem- 5-10 ml decoction; API Vol. II

Fruit Powder: 5 to 10 grams

Powder of the Stem: 3 to 6 Grams

Root bark juice: 12 to 24 mL

Tincture: 2 to 5 ml to be taken 15 to 20 minutes before meal, thrice a day 

Tea: To make tea, take 2 to 4 grams of Barberry root or 1 to 2 teaspoonful berries, steep in 150 ml of water for 10 to 15 minutes. Take one cup three times a day. It can be used as mouth wash or for gargle to allay sore throat.

Dry Extract:  250 to 500 mg three times a day

Ointment: To make ointment use 10% extract. For psoriasis apply three times a day
For older patients (above 65 years of age) use lower doses

Rasaanjana

Daarwyaadi Kwaath: 10 to 20 ml. once or twice a day, before or after food as directed by Ayutvedic doctor

Daarwyaadi Kashaaya: 10 to 20 ml. once or twice a day, before or after food as directed by Ayutvedic doctor. [133]

Daarwyaadi Leha: Dose not found

Dashaanga Lepa

Daarwyaadi Taila

Capsules

Daaru-Haridraa paste is used for conjunctivitis. In ophthalmic conditions the paste is applied around eyes. It is also use to treat chancroid ulcers, goiter, fistula and erysipelas.

Daaru-Haridraa rasaanjan combined with rose water is used to treat ear ache and ear discharge.

Daaru-Haridraa douche is used to treat vaginal discharges. [134], [135], [136] 

Rasaut: A very valuable preparation Rasaut is prepared from Daaruharidraa. For preparing Rasaut, the bark of the root and of the lower part of the stem is boiled in water. The solution is then strained and evaporated till a semi-solid mass, Rasaut, is obtained. Rasaut is freely soluble in water. It is mixed with butter and alum or with lime-juice or opium and is applied externally to the eyelids to cure ophthalmia and other eye diseases. It is mild laxative, tonic and is useful in curing ulcers and fevers. [137]



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Unknown said…
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