Daaru-Haridraa (Berberis aristata)

Daaru-Haridraa (Berberis aristata)

Introduction

Daaru-Haridraa AKA Barberry in the West is a common garden bush. Daaru- Haridra (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. Early physicians thought that the yellow wood of Barberry could allay jaundice. This belief was based on the philosophy of the doctrine of signatures. Native American Indians used Daaru-Haridraa in cases of general debility and as an appetizer. The colonists used the root of the herb as bitter tonic. In traditional folk medicine, Barberry is used to improve appetite, to treat fever, diarrhea and to increase vitality. [1]. [2]

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. [3]

Other Names

Latin/Botanical/Scientific: Berberis aristata
Sanskrit: Daaru-Haridraa, Daaru-Peetaa, (Peetaa-Daaru?), Darvi,  
English: Indian Berberry
Bengali: Daaruharidraa
Gujarati: Daaru-Haldar.
Hindi: Daaru-Haldee, Kashmal, (According to indiabiodivesrsity.org)  Chitra
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  

Taxonomic Classification

Kingdom: Plantae
Unranked: Angiosperm (According to indiabiodivesrsity.org) Phylum: Tracheophyta)
Unranked: Eudicots
Division: Magnoliophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Berberidaceae
Genus : (According to indiabiodivesrsity.org : Berberis)
Species : (According to indiabiodivesrsity.org : Berberis aristata 

 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. [6]  

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. [7]

Plant Morphology

      

                   Plant                                       Root



      

                  Stem                                        Leaves               


     
 
         Flowers                                           Fruits



Seeds

Images of Daaruharidra (Berberis aristata)
  
Macroscopic Characteristics

Daaruharidra is a large, deciduous, erect spiny shrub, growing in thick horny clumps reaching between 3 and 8 feet in height. The roots and stems are burgeoning (flourishing) with the potent alkaloid berberine, making its stems appear to be ‘Turmeric-colored’.  [11]

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 (rupture of cells or tissues) hard and tough

Stem is red when the plant is young, getting darker as the plant grows older. It is 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. It is 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 stalked, complete, hermaphrodite and yellow in color. They form a simple corymbose or racemose inflorescence with 11 to 16 flowers per raceme. They are arranged along a central stem. The Calyx yellow in color having 3 large and 3 small sepals which are yellow in color, actinomorphic (i. e. characterized by radial symmetry, such as a starfish or the flower of a daisy), caduceus (the staff carried by Hermes in Greek mythology) or caducous (an organ or part easily detached and shed at an early stage), 4 to 5 mm long. The Corolla is polypetalous with 6 petals, yellow 4 to 5 mm long. The Androecium (the male reproductive structure) is polyandrous, adnate (attached squarely and firmly to the stem), contains 6 stamens and are 6 mm long. The Gynecium (the female reproductive structure) is one, 4 to 5 mm long with a short style and a broad stigma.   

The plant flowers between March and April.

Fruits are edible berries, succulent, bright red in color, ovoid, smooth, acidic when raw, rich in vitamin C, have medicinal properties. The berries are 7 mm long and 4 mm in diameter, weighing about 227 mg and 237 ml in volume, aconite violet in color. They start ripening from the second week of May and continue to do so throughout June.

Seeds two to five in number, varying in color from yellow to pink, each weighing about 25 mg and about 29 ml in volume. [12], [13], [14], [15], [16], [17]

Microscopic Characteristics

Stem- Shows rhytidoma (outer bark) with cork consisting of 3-45 rectangular, yellow colored, thin-walled cells, arranged radially. The sieve elements are irregular in shape, thin-walled, a few cells containing yellowish-brown contents. The  phloem fibers are 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. The stone cells are 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. The secondary phloem is a broad zone, consisting of sieve elements and phloem fibers, traversed by multi seriate phloem rays. The   sieve elements are arranged as tangential bands and tangentially compressed cells alternating with single to five rows of phloem fibers. The phloem fibers short, lignified, thick-walled having pointed ends. The secondary xylem are broad consisting of xylem vessels, tracheids, xylem fibers and traversed by multi seriate xylem rays. The xylem vessels are numerous, small to medium sized, distributed throughout xylem region in singles or in groups. The groups of vessels are usually arranged radially. The isolated vessels are cylindrical with rounded or projected at one or both ends with spiral thickening. The xylem fibers numerous, lignified, large, thick-walled with wide lumen and pointed tips. The xylem rays are quite distinct, straight, multi seriate, consisting of radially arranged rectangular cells, each ray 30-53 cells high, 8-12 cells wide. Few ray cells contain brown contents.       

Powder- Yellow in color shows mostly fragments of cork cells, sieve elements, yellow colored phloem fibers which are entire or in pieces. The stone cells are in singles or in groups. There are numerous prismatic crystals of calcium oxalate. The xylem vessels have spiral thickening. They are thick-walled, lignified xylem fibers and ray cells. [18], [19]
 
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. [20] 

Parts Used

Bark, root, stem, seed and fruit.
  
Rasaut/ Rasaanjana: Root bark and lower stem are boiled with water, strained and condensed till a semi solid mass is obtained which is known as Rasaut. The extract called Rasaanjana is also used for medicinal purpose.  

Phytochemistry

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, epiberberine, oxyberberine, berberrubine, beraromoline, protoberberine (Karachine), dihydrokakarachine,  taximaline, palmatine, jatrorrhizine, oxycanthine, bervulcine, columbamine, isotetrandine and vulcracine, dehydrocaroline, pakistanine, 1-O methyl pakistanine, pseudo palmatine chloride and pseudoberberinr chloride.

Pharmacological actions of almost all chemical constituents of B. aristata are same as those of berberine. Hence pharmacology of berberine is discussed in detail.

Other ingredients:  
Carbohydrates, organic acids like chelidonic acid, citric acid and malic acid, resin, tannin, pectin, polyphenolic compounds, some vitamins and mineral elements [21], [22]


Identity, Purity and Strength
(1)
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 [23]

(2) Standards accepted by I. P. in 2010

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 12.0 percent determined on 5.0 g by drying in oven at 1050 (scale not mentioned)
Microbial contamination: Complies with the microbial contamination tests.
Assay: Standardized as determined by liquid chromatography.

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.

Storage: Should be protected from heat, moisture, attack of insects and rodents. [24]

Cytological Identity

The number of chromosomes in Daaruharidraa (Berberis aristata DC) is 6 [25]

Genetic study
With the help of molecular techniques like Random Amplified Polymorphic DNA (RAPD), Amplified Fragment Length Polymorphic DNA (AFLP), Restricted Length Polymorphic DNA (RFLP) and Inter Simple Sequence Repeat (ISSR) etc, the identification of plant species has now become very accurate. [26]

Safety Tests

No safety data for each specific species of herb is available. Here are general guidelines: 

Heavy Metals:
Arsenic:          Not more than 5.0 mg/kg
Mercury:        Not more than 0.5mg/kg
Lead:              Not more than 10.0 mg/kg
Chromium:    Not more than 0.3 mg/kg

Microbial Limits:
Total bacterial count:                                  Not more than 105cfu/g
Total yeast and mould count:                      Not more than 104cfu/g
Bile tolerant gram negative bacteria:         Not more than 104cfu/g

Specific Pathogens:

Salmonella spp:                        Absent in 25 g
Escherichia coli:                      Absent in 1g   
Staphylococcus aureus:          Absent in 1g          
Pseudomonas aeruginosa:      Absent in 1g [27]

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)

Susruta 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 [28]

It is anti-inflammatory (shothaghna) and analgesic on topical application, vulnerary (heals wounds), antipruritic, liver stimulant, appetizer, antidiarrheal, laxative, antitussive (kaasaghna), anti-asthmatic, styptic (stops bleeding), raktashodhana (blood purifier), rasaayana (rejuvenating and adaptogenic).

As its properties resemble to those of Haridraa (C. 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 (B. 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 (rejuvenating and adaptogenic) [29], [30], [31]

Modern View

B. aristata is anti-inflammatory, anti-pyretic, analgesic, antiscorbutic, antiseptic, vulnerary, appetizer, laxative, hepatoprotectant and emmenagogue.

Berberine

Molecular formula: C20H18NO4                        
Structural formula:




 [32]



Berberrine is a strongly yellow colored, crystalline alkaloid. Under UV light berberine shows a strong yellow fluorescence. Berberine is a quaternary ammonium salt from protoberberine group of isoquinoline alkaloids. [33]

Phytopharmacology of berberine is also described in detail in the chapter on Guduchee (T. cordifolia)


Pharmacodynamics/ Pharmacokinetics of Berberine
      
No pharmacokinetic data on animal studies about Daaruharidraa (Berberis aristata) is available. However, in humans, oral administration of 1.2 g of berberine significantly delays small intestinal transit time. [34]

Absorption: Eight hours after administration of 500 mg/ kg of berberine to infant rabbits, the blood concentration was 0.8 microgram/ml. Berberine can be absorbed through skin [35]

Metabolism: Peak concentration of berberine reaches after 12 hours in the muscles and liver.

Distribution: In rats, after the oral dose of 0.1g/kg maximum serum concentration is 0.083mcg/ml and time to maximum concentration is 2.4 hours. The blood levels plateau at 4 to 24 hours. [36]

Excretion: 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. [37], [38]

Anti-inflammatory activity of Berberine

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.

Berberine significantly decreases leukotriene formation and monocyte production. It inhibits PGE2 generation by monocytes.

By decreasing vascular permeability, berberine inhibits inflammatory edema. [39]

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. [40]

Immunomodulating activity of Berberine

Berberine shows significant inhibition of mitogen induced lymphocyte transformation.

Berberine inhibits neutrophil adherence and chemotaxis. [41]         

Anti-microbial activity of Berberine

Berberine has significant anti-microbial activity against Gram positive and Gram negative bacteria and fungi. [42]

In vivo study with white mice berberine showed antibacterial activity against Streptococcus pneumoniae. [43]
  
In vitro (in mice) methyl extract of berberine demonstrated ‘cidal’ activity against T. vaginalis, G. lamblia, and E. histolytica. [44]

Berberine sulphate is bactericidal against Vibrio cholera at 35 mcg/ml concentration, against Staphylococcus aureus at 50mcg/ml concentration and Streptococcus pyogenes at 30mcg/mL concentration. Berberine also shows anti-bacterial activity against Escherichia coli, Shigella dysenteriae, Salmonella paratyphi and various Klebsiella species. Berberine sulphate also exhibits antimicrobial activity against Gram-positive, Gram-negative bacteria, fungi and protozoal organisms through the inhibition of RNA and protein synthesis. [45], [46]

In an in vitro study, berberine was shown to suppress the growth of Helicobacter pylori in a dose dependant manner. [47]

Actions of Berberine on Nervous System

To evaluate cholinergic activity of berberine, in one study, berberine was administered to rats at the dose of 0.1 g/kg and 0.5/kg for 14 days. This treatment improved scopolamine-induced amnesia in rats. This effect was augmented by physostigmine and neostygmine. [48]

Berberine has muscle relaxant effect on smooth muscles. In one study at the dose of 20mcg/kg body weight berberine sulphate blocked the response of ileum, trachea and rectal muscles to acetylcholine. [49]
In animal study berberine sulphate produced sedation and potentiated the sedative effects of pentobarbitone. [50]
In mice berberine has shown to lower rectal temperature, reduce spontaneous motor activity and prolong hexobarbitone-induced sleeping time. [51]
Actionsons of Berberine on Endocrine System

In an animal study berberine has been shown to inhibit parathyroid hormone-stimulated bone resorption. At doses of 30-50mg/kg/day berberine prevents the decrease in bone mineral density of lumbar vertebrae in oophorectomised rats and induces apoptosis of osteoclastic cells. [52]

Actions of Berberine on GI system:

Given orally to mice at doses of 0.06 mg to 20 mg/kg daily decreases the frequency of purging by delaying intestinal motility. In mice at doses of 40 and 80 mg/kg bodyweight berberine sulphate decreases the occurrence of purging induced by castor oil. [53], [54]

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

In experimental studies berberine reduced the secretion of water, sodium, chloride and bicarbonate induced by cholera-toxin in rat ilea. It also inhibited the secretary response to E. coli enterotoxin.

Results suggest that the antidiarrheal property of berberine is mediated via its ability to delay the small intestinal transit. [55], [56], [57]

Actions of berberine on hepato-biliary system:

Berberine increases the secretion of bilirubin in rats with hyperbilirubinemia but this effect diminishes on continued administration of berberine. [58]

However a recent study shows that berberine displaces bilirubin from albumin in both in vitro and in animal studies, resulting in an increase in serum total and direct bilirubin concentrations. [59]

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. [60]

CCl4 is a known hepatotoxic agent. The CCl4 toxicity is manifested by elevation of liver enzymes and histological changes in the hepatic tissue. On administration of berberine the elevated levels of liver enzymes come to normal and histological study shows reversal of the damage. Berberine at the dose 10mg/kg markedly attenuates the expression of TNF-α, COX-2 and iNOS. Thus berberine inhibits the inflammatory response of CCl4 toxicity in the liver. [61]

At doses of 2mg/kg intramuscularly or 3mg/kg orally thrice a day berberine prevents the development of amoebic hepatitis in hamsters. [62]

For in vitro study of anti-hepatitis B activity of berberine, HepG2.2.15 cell model was selected. The result of the study revealed that berberine can inhibit hepatitis B virus in vitro. The antiviral effect may be related to AP-1 up-regulation and CHOP down regulation. Further study is necessary to confirm the mechanism of anti-hepatitis B activity of berberine. However in Feb. 2010, the researchers have applied for patent for this work. [63]

On Feb 20, 2013, the application for a patent (Code No C12) was rejected. [64]

The precise mechanism of development of non alcoholic fatty liver disease (NAFLD) is not understood. Obesity, dyslipidemia, insulin resistance, deposition of intra hepatic fat and inflammation are crucial players in the process of NAFLD. NAFLD is the hepatic manifestation of obesity and metabolic syndrome.

By correcting hyperlipidemia, berberine strongly reduces storage of fat in the liver. Treatment with berberine for sixteen weeks alleviates hepatic steatosis. Berberine also reduces hyperlipidemia in statin-intolerant subjects. Diabetes predisposes to steatosis. Berberine reduces the insulin resistance, controls diabetes, and prevents hepatic steatosis. Further berberine prevents the development of obesity, insulin resiastance and reverts hypertriglycerinemia to normal levels. Thus berberine prevents and arrests the progression of fatty degeneration of the liver. Investigations show that berberine supplement reduces alanine and aspertate transaminases in type 2 diabetes, indicating the restoration of liver function. Furthermore, berberine has been shown to reduce liver necrosis in NAFLD and in steatosis due to hepatitis C infection. The recent literature suggests that berberine may be integrated into glucose and lipid regulation for combating NAFLD and metabolic syndrome. [65]

Actions of berberine on Cardiovascular System (CVS)

Berberine extract inhibits adrenalin-induced aortic contraction, improves the left ventricular function in dogs with failing heart, decreases the peripheral resistance, increases significantly the cardiac output and ejection fraction. It also exhibits anti-arrhythmic activity and restores normal sinus rhythm. [66]

The bolus dose of 1mg/kg of berberine sulfate injection administered to rats one minute after undergoing coronary artery occlusion significantly reduced early mortality from ventricular fibrillation. [67]

Berberine sulfate decreases the blood pressure in experimental animals. The effect is dose-dependent. This hypotension is not inhibited by atropine, mepyramine maleate, propranolol and phenoxybenzamine.  [68]

In rats at 20mg/kg berberine inhibits platelet-activating factor. It inhibits platelet aggregation caused by ADP, arachidonic acid and collagen. [69]

Antineoplastic activity of berberine

Berberine inhibits etoposide and campothecin induced DNA fragmentation and apoptosis of thymocytes.

Berberine inhibits activator protein-1 activity which is essential for carcinogenesis.
After 3 days of continuous exposure in vitro, berberine significantly inhibited hepatoma cell growth in a dose-dependent manner. It also inhibited the release of α fetoprotein after 18 hours of exposure.  [70]

 Oxyberberine  
Molecular formula: C20H17NO5
Structural formula:



Oxyberberine and berlambine are synonyms. Pharmacology of oxyberberine is similar to that of berberine.  [71]

Berbamine
Molecular formula: C37H40N2O6
Structural formula:





Berbamine is anti-inflammatory and anti-oxidant. It prevents ventricular fibrillation by means of inhibition of sodium and calcium overload. It exhibits anti-arrhythmic effect. It is calcium channel blocker and vasodilator. [72], [73], [74]

At the dose of 25 mg/kg dose berbamine shows immunosuppressant effect. [75]

At 10mg/kg dose berbamine inhibits neutrophil adherence and chemotaxis.

At higher doses splenic cells are suppressed. Berbamine significantly inhibits mitogen induced lymphocyte transformation. [76]

Berbamine inhibits the tumor necrosis factor and platelet activating factor in a dose dependant manner. [77]

Berberrubine (Hydrochloride)
Molecular formula: C19H16NO4
Structural formula:




Pharmacology of berberrubine hydrochloride is similar to that of berberine, but berberrubine hydrochloride has predominantly anti-tumor activity. [79]

Aromoline

Molecular formula: C36H38N2O6
Structural formula:


  [80]

Pharmacology of aromoline is similar to berberine. In addition it shows vasodilator, anti-hihtaminic, anti-amoebic and anti-plasmodial activity. [81]


Protoberberine (Karachine)
Molecular formula: C26H27NO5
Structural formula:


                                                                                                                                                                                                                                                                                                 [82], [83]


 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. [84]

In a comparative study protoberberine was shown to inhibit lipoxygenase and lipid peroxidation leading to its antioxidant properties. The antioxidant activity of oxyberberine, corytuberine and columbamine is stronger than berberine. [85]

Protoberberine alkaloids showed anti-hepatitis B actions when tested with HepG2.2.15 cell line in vitro. [86]

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. [87], [88]

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 multidrug resistant (MDR) cancer cells. Its synthetic derivative has stronger antibacterial activity.  [89]

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. [90], [91]

Oxycanthine

Molecular formula: C37H40N2O6   [91] 

Structural formula:



Oxycanthine is also spelled as Oxyacanthine. Oxycanthine exhibits anti-bacterial activity. Its pharmacological actions are similar to that of berberine but oxycanthine is much less effective. [92]

Columbamine

Molecular formula: C20H20NO4
Structural formula



   
                                                                                             
[93]

Columbamine inhibits proliferation and neovascularization of metastatic osteosarcoma. Columbamine induces cell cycle arrest at the G2/M transition. Columbamine inhibits U2OS cell-mediated neovascularization. Thus Berberis aristata that contains columbamine can be a future anticancer drug.  [94]

Isotetrandine
Molecular formula: C38H42N2O6

Structural formula:





Isotetrandrine can enhance the cytotoxicity of doxorubicin. Researchers suggest that isotetrandrine might become a candidate for multidrug resistant cancers. [96]
 
Some Testiminials from Modern research

Hepatoprotective Activity

Berberine is the prime important pharmacologically active molecule in all the species of Berberis. Hence the pharmacology of Daaruharidraa (Berberis aristata) is the pharmacology of berberine. It is described in detail above. However in the experimental studies where all parts of the herb are used to observe the pharmacological actions are described here.

Berberis aristata protects the liver from CCl4 toxicity. This activity is mediated through inhibition of microsomal drug metabolizing enzyme. [97]

Often Berberis vulgaris and Berberis aristata are used as synonyms for Barberry. Berberis vulgaris exhibits anti-hepatitis C activity. This effect is attributed to immunostimulant potential as it enhances the phagocytic activity of mononuclear cells in the blood. [98]

To evaluate anti-cirrhotic activity of Daaruharidraa (Berberis aristata), cirrhosis was induced in rats by using Dimethylnitrosamine. The cirrhosis was proved by elevated liver enzymes, hematological abnormalities and histological changes. The oral administration of Ethanolic Extract of Berberis aristata (EEBA) and Aqueous Extract of Berberis aristata (AEBA) at the dose of 200mg/kg, decreased the size of cirrhotic nodules, improved the biochemical and hematological parameters. These results were compared with the dose of 100mg/kg of silymarin, the standard drug used as a hepatoprotectant. The results showed that EEBA and AEBA exhibit anti-cirrhosis activity similar to silymarin. However EEBA is more effective than AEBA.[99]

In one study Earlich-Ascites-Carcinoma was induced in Swiss albino mice by injecting 106 cell/ml of tumor cell suspension. EEBA and AEBA were used to treat these animals. Daaruharidraa (Berberis aristata) improved the general condition of the animals. The animals gained weight. The survival of the animals was prolonged. But these results were inferior to the anti-tumor effect of 3.5 mg/kg dose of cisplatin.  Of the two extracts of Daaruharidraa (Berberis aristata), EEBA was more effective. [100]

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. [101]

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 (bleeding disorder), 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).

 

Daarwyaadi Ghana Sattwa watee (Tablet from Ayurvedic Medicine): has been used in Shwetapradara (Leucorrhea) and other diseases.    

 

Ayurvedic practitioners use it to treat jaundice, enlargement of liver and spleen (portal hypertension). [102]


Usages in Modern Medicine
  
B. 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 (T. 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     [103]

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 B. 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 B. 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 (Water decoction): 10 to 20 ml. once or twice a day, before or after food as directed by Ayutvedic doctor

Daarwyaadi Kashaaya (Water decoction): 10 to 20 ml. once or twice a day, before or after food as directed by Ayutvedic doctor. [104]

Daarwyaadi Leha (Paste for oral use): Dose not found

Dashaanga Lepa (Paste for External Application)

Daarwyaadi Taila (Oil preparation)

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. [105], [106], [107]

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. [108]


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