Brahmi ( Bacopa monneiri) Part 2

                                                             Brahmi   ( Bacopa monneiri)      Part 2                               

Phytochemistry

The phytochemistry of Brahmi (Bacopa monnieri) has been extensively studied. The phytochemicals present in the plant are:

 

Saponins called “bacosides” Bacosides are a complex mixture of structurally closely related compounds, glycosides of either jujubogenin or pseudojujubogenin. Bacosides comprise a family of 12 known analogues. They are grouped as major bacopasaponins and minor bacopasaponins. Major bacopasaponins are: bacosides A3, bacopaside II, bacopaside I, bacopaside X,  bacopaside N2, bacopasaponin C. Minor components are: bacopasaponin E, bacopasaponin F, bacopaside N1, bacopaside III,  bacopaside IV and bacopaside V.   

 

Hersaponin

 

Five cucurbitacins: bacitracin A to E.

Three phenylethanoid glycosides: monnieraside I-III. They are isolated from aerial parts of Brahmi (Bacopa monnieri).

Plantioside B

Two dammarane jujubogenin bisdesmosides bacopasaponins E and F  

Sterol glycoside bacosterol-3-O-beta-D-glucopyranoside

A new Matsutaka alcohol derivative, (3R)-l-octan-3-γl-(6-O-sulphonyl)-beta-d-glucopyranoside

Two flavonoids: leuteolin and apigenin,

Alkaloids: brahmine, nicotinine and herpestine

Brahmi (Bacopa monnieri) also contains betulinic acid, D-mannitol, stigmastanol, β-sitosterol and stigmasterol

----Shalini Lal et al, Phytochemical and Pharmacological Profile of Bacopa monnieri-An Ethnomedicinal Plant, International Journal of Pharmaceutical Sciences and Research, (2019), 1-230

----https://shodhganga.inflibnet.ac.in/bitstream/10603/172494/10/10_chapter%204.pdf

 

Identity, Purity and strength as per international guidelines

 

Foreign matter: Not more than 2 percent

Total Ash: Not more than 18 percent

Acid-insoluble Ash: Not more than 6 percent

Sulfated ash: Not more than 20 percent

Alcohol-soluble extractive: Not more than 6 percent

Water soluble extractive: Not less than 15 percent

Loss on drying: Not more than 14 percent

 

The Ayurvedic Pharmacopoeia of India Part-1, Volume-II

 

 

 

 

Heavy Metal Analysis as per international guidelines

 

Element                     Permissible Limits

 

Arsenic                 Not more than 5 to 10 mg/kg

Cadmium              Not more than 0.03mg/kg    

Lead                      Not more than 5 to 10 mg/kg                   

Mercury                Not more than 0.5 mg/kg

Chromium            Not more than 0.3 mg/kg

 

Permissible Microbial Load as per international guidelines

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: (as per international guidelines)

 

Salmonella species:                 Absent in 25 g /none

Escherichia coli:                      Absent in 1g / maximum 102 to 104 per gram 

Staphylococcus aureus:          Absent in 1g          

Pseudomonas aeruginosa:      Absent in 1g

Shigella species:                                      

Enterobacter species:            maximum 104 per gram 

Other enterobacteria:            maximum 103 per gram

Aerobic bacteria:                  maximum 105 to 107 per gram  

Mould propagules:               maximum 103 to 105 per gram    

Yeasts and Mould:               maximum 103 to 104 per gram    

  

Aflatoxins (as per international guidelines)

 

Aflatoxin B1, Aflatoxin B2, Aflatoxin G1, Aflatoxin G2                      

Preferably Aflatoxins should be below detectable limits (BLD)

 

----Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.

----https://apps.who.int/medicinedocs/en/d/Js4927e/21.html

 

 

Pesticide residues (as per international guidelines)

 

In recent times various pesticides are used to protect and preserve the food and medicinal values of plants.

To avoid toxicity of herbal medicine, International Society for Standardization of Drugs and World Health Organization (WHO) have laid the guidelines for permissible levels of pesticides in herbal medicines.

In general, the pesticide contamination in any herbal medicine should be less than 1 percent of total intake from all sources, including food and drinking water.

Aldrin and dieldrin are broad spectrum pesticides commonly used in agriculture. The recommended maximum limit of these pesticides is Not more than 0.05 mg/kg.

----Guidelines for predicting dietary intake of pesticide residues, 2 nd review edition, Geneva, World Health Organization, 1997

----European pharmacopoeia, 3rd edition Strasbourg, Council of Europe, 1996  

 

Radioactive residues (as per international guidelines)

 

A certain amount of exposure to ionizing radiation of plants cannot be avoided since there are many sources, including radionuclides occurring naturally in the ground and the atmosphere.

The World Health Organization (WHO), in close collaboration with several international organizations, has developed guidelines for permissible and acceptable limits for radioactive residues in herbal medicines.

The amount of radiation in plants depends on intake of radionuclides. Significant risk is associated only with consumption of quantities over 20 kg of plant material per year so that the risk to health is most unlikely to be encountered given the amount of medicinal plant materials need to be ingested. Additionally, the level of contamination might be reduced during the manufacturing process. Therefore World Health Organization (WHO) has not proposed strict limits regarding the acceptability for radioactive contamination.

 

Quality control methods for medicinal plant materials, Geneva, World Health Organization, 1998 

 

Genetic Identity/ DNA sequencing

 

For medicinal purposes, it is wont to select Brahmi (Bacopa monnieri) on the basis of morphological characteristics such as: leaf color (green, dark green and yellow-green), stem (thickness and color), leaf size (large >70 mm2; medium 60-70 mm2; and small 50-60 mm2) and plant type (spreading or semi-erect). However morphological identity is inadequate because of look-alike herbs. More over morphological characters may not be obvious at all stages of the development of the plant and appearance may be affected by the environment. Also there is a high genetic variability in the population.

 

To overcome these hindrances, scientists have devised: SSR (Simple Sequence Repeat), AFLP (Amplified Fragment Length Polymorphism), RAPD (Random Amplified Polymorphic DNA), ISSR (Inter Simple Sequence Repeats), RFLP (Restriction Fragment Length Polymorphism), PIC (Polymorphic Information Count), DNA (Deoxyribonucleic acid), PCR (Polymerase Chain Reaction), UPGMA (Unweighted Pair Group Method with the Arithmetic Averaging Algorithm) and PCA (Principal Component Analysis) methods for accurate molecular identity of Brahmi (Bacopa monnieri).

     

Niraj Tripathi et al, Assessment of genetic variations among highly endangered medicinal plant Bacopa monnieri (L.) from Central India using RAPD and ISSR analysis, 3Biotech Volume 2, pages 327-336, 2012

 

Chromosomal Identity

 

The chromosome number reported in Brahmi (Bacopa minnieri) is 2n=64 

 

Samaddar T. Nath et al, Karyotype analysis of three important traditional Indian medicinal plants, Bacopa monnieri, Tylophora indica and Withania somnifera, The Nucleus, 55, 17-20    

Ayurvedic properties

Rasa (Taste): Madhura (Sweet), Tikta (bitter), Kashay (astringent) 

Weerya (Potency): Sheeta (Cooling)

Wipaaka (Metabolic property after digestion): Madhura (sweet)

Guna: Laghu (Light), Sara (Laxative)

----Bhawaprakaash Nighantu shlokas 280-281

----https://www.amilpharmaceuticals.com/herbs/brahmi/

Gana:

Charaka: Prajasthapana gana

Sushruta: Veeratharvadi gana

 

Warga:

 

Bhavaprakash Nighantu: Guduchyaadi varga

Dhanwantari Nighantu: Karaveeradi varga

Kaiyadeva Nighantu: Oshadi varga

Raja Nighantu: Parpatadi varga

Priya Nighantu: Shatapushpa varga

Madanapala Nighantu: Abhayadi varga

Nighantu aadarsha: Tikta lonika varga

Shodala Nighantu: Karaveeradi varga

Hridaya Deepika Nighantu: Deepana varga

Shaligrama Nighantu: Guduchyaadi varga

Dravyaguna Vignyan (P.V. Sharma): Medhyaadi varga

 

Ashalatha M and L. N. Shenoy, A critical Review on Brahmi, http://www.iamj.in/posts/images/upload/141_152.pdf

 

Effects on Doshas: Waatahara, Pittakara, Kaphakara. Balances all doshas

Effects on Dhatus: Balances all dhatus

Effects on Srotasas: Balances all srotasas. It prominently exerts its action on the nervous system. Being a neurotropic agent, it is beneficial in neurologic and psychiatric disorders. It has sedative as well as stimulant nervine effects

 

Brahmi: “Herb of Grace”, Calofornia College of Ayurveda, www.ayurvedacollege.com>Ayurveda life    

 

Ayurvedic actions (Karma)

 

Medhya: Beneficial for intellect, promoting intelligence

Prajnyasthapana: Stabilizes intellectual power

Matiprada: Gives knowledge

Smrutiprada: Increases memory

Mohahara: Antagonizes greed, abnormal longings 

Aayushya: Promoting longevity

Jeevaneeya: Improves life energy

Rasaayana: Rejuveniting

Vayasthapaka: Stabilizes age

Balya: Improves physical and mental strength

Swarya: Beneficial for voice, Relieves hoarseness of voice, Improves quality of voice

Majjadhatu Rasaayana: Rejuvenates bone marrow, Rejuvenates nervous system

Nidrajanana: Induces sleep

Unmaadad: Treats neuroses, Mania, Psychosis

Apasmaara: For the treatment of epilepsy

Kaasaghna: Antitussive, Useful for the treatment of bronchitis

Hridya: Beneficial to heart

Warnya (Varnya): improves complexion

Shothhara: Anti-inflammatory, Relieves edema

Deepana: Appetizer

Anulomana: Prokinetic, Antiflatulent, Carminative

Kushthaghna: Antileprotic, Useful for the treatment of skin diseases

Pandu: Treats anemia

Pleehawridhi: For the treatment of splenomegaly

Meha: Treats diabetes

Vishaghna/Vishahara: Useful for the treatment of poisoning

Arsha: Treats Piles, Anal fissures

Jwara: Treats fevers (PUOs)

Ruk: Analgesic, Relieves pain

Kandughna: Antipruriric

 

----The Ayurvedic Pharmacopoeia of India Part-1, Volume-II

----Ashalatha M and L. N. Shenoy, A critical Review on Brahmi, http://www.iamj.in/posts/images/upload/141_152.pdf

 

Modern View

Bacosides

Bacosides are a complex mixture of structurally closely related compounds, glycosides of either jujubogenin or pseudojujubogenin. Bacosides comprise a family of 12 known analogues. They are grouped as major bacopasaponins and minor bacopasaponins. Major bacopasaponins are: bacosides A3, bacopaside II, bacopaside I, bacopaside X,  bacopaside N2, bacopasaponin C. Minor components are: bacopasaponin E, bacopasaponin F, bacopaside N1, bacopaside III,  bacopaside IV and bacopaside V.  

 

Shalini Lal et al, Phytochemical and Pharmacological Profile of Bacopa monnieri-An Ethnomedicinal Plant, International Journal of Pharmaceutical Sciences and Research, (2019), 1-230

 

Bacoside A

Molecular Formula: C41H68O13 (Pubchem)

Structural Formula:

 

 

 

 

Bacoside A is a mixture of chemical compounds known as bacosides. Its major constituents include bacoside A3, bacoside II (jujubogenin isomer of bacopasaponin C) and bacopasaponin C. The mixture has been studied for its potential of neuroprotectivity in in vitro experiments and animal models.

https://en.wikipedia.org/wiki/Bacoside_A

Bacoside B was found to be identical to Bacoside A in respect to their carbohydrate and aglycone moieties. But bacoside A is levo-rotatory and bacoside B is dextro-rotatory. Both are nootropic. Pharmacologically, bacoside A is more active than bacoside B 

M. Deepak and A. Amit, The need for establishing identities of ‘bacosides A and B’, the putative major bioactive saponins of Indian medicinal plant Bacopa monnieri, Phytomedicine,11:264-268m 2004

 

Recent clinical trials indicate that bacosides exert their neuroprotective actions through modulating antioxidant enzymes, namely, superoxide dismutase (SOD), catalase etc. they also regulate the levels of different neurotransmitters in the brain. Hence they are useful for the treatment of Alzheimer’s disease and epilepsy. Interestingly bacosides do not exert any side effects in animal models and human volunteers.

Usual dose of bacosides is 15 to 30 mg 3 times a day

 

Sukanya Majumdar et al, Bacosides and Neuroprotections, Natural Products,

First online 15 May 2013, pp 3639-3660, https://link.springer.com/referenceworkentry/  

 

Administration of alcoholic extract of Brahmi (Bacopa monnieri) prevented the scopolamine (3mg/kg bodyweight), sodium nitrite (75mg/kg body weight) and BN52021 (15 mg/kg body weight) experimental amnesia induced in mice. This effect of improving antegrade amnesia induced by scopolamine and sodium nitrite was possibly by improving acetylcholine level and hypoxic conditions respectively. The effect of improving amnesia was attributed to bacosides present in Brahmi (Bacopa monnieri). Besides this bacosides also reversed BN52021 induced retrograde amnesia, probably due to increase in platelet activating factor (PAF) synthesis by enhancing cerebral glutamate level. From these studies it can be said that bacosides and entire Brahmi (Bacopa monnieri) plant are not merely memory enhancers but can be useful for the treatment of amnesias arising from various causes.

 

Komal Kishore et al, Effect of bacosides, alcoholic extract of Bacopa monnieri Linn. (brahmi), on experimental amnesia in mice, Indian J of Exp Biol. 2005 Jul; 43 (7): 640-5  

 

Brahmi (Bacopa monnieri) and bacosides are extensively used as neuromedicine for the treatment of various disorders such as anxiety, depression and memory loss. Chemical characterization studies showed that powerful antioxidant and free radical scavenging activity of bacoside A is vital for this neuroprotection. Free radical scavenging, suppression of lipid peroxidation and activation of antioxidant enzymes by bacosides help to attain a physiological state of minimized oxidative stress. The neuroprotective activity of bacosides is attributed to the regulation of mRNA (messenger ribinucleic acid) translation and surface expression of neuro-receptors such as AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, also known as AMPA receptor or quisqualate receptor), NMDAR (N-methyl-D-aspartate receptor, also known as NMDA receptor) and GABAR (Gamma aminobutyric acid) in various parts of the brain. The binding of bacosides to these receptors is controlled by BBB (Blood Brain Barrier).

[Note: AMPAR and NMDAR are glutamate receptors. Glutamate is involved in learning process.]  

 

Vini C. Sekhar et al, Insights into the Molecular Aspects of Neuroprotective Bacoside A and Bacopaside, Curr Neuropharmacol 2019 May 17(5):438-446

 

Cognitive impairment is a debilitating symptom of schizophrenia, Alzheizemer’s disease etc. Brahmi (Bacopa monnieri) or bacoside A and B could be novel nueroprotective agents. They can not only prevent the memory loss but help to restore the memory loss. They exert their action via Vesicular Glutamate Transporter 2 (VGLUT 2) in cingular gyrus  

 

T. Wetchateng et al, EPA-0117-The use of bacosides a and b to prevent a cogniticve deficit in schizophrenia rat models resulting in increased vesicular glutamate transporter 2 (VGLUT2) in cingular gyrus, European Psychiatry, Volume 29 Supplement 1 2014 Page 1

 

Brahmi (Bacopa monnieri) at a dose of 40 and 80 mg/kg bodyweight is found to be useful in the treatment of neuropathic pain. This result is comparable to the effect of 75mg/kg bodyweight of gabapentin. The effect is attributed to bacoside a and b.

 

Muhammad Shahid et al, A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats, BMC Complimentary and Alternative Medicine volume 17, Article number: 293 (2017)   

 

 

 

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