Table Info

Table 1.

Some neuroprotective phytochemicals from the medicinal plants Withania somnifera, Bacopa monnieri, and Centella asiatica, their actions and the mechanisms of their actions

Plant	Neuroprotective phytochemicals		Neuroprpotective action	Mechanism of action
Plant	Phytochemicals	Chemical nature	Neuroprpotective action	Mechanism of action
Withania somnifera	Anaferine	Alkaloids	Protection against neurodegenerative diseases like Huntington’s disease, Parkinsonism, Alzheimer’s disease [24]	GABA mimetic action that promotes dendrites formation [19]
	Withanolides	Steroidal lactones
	Anahygrine	Alkaloids
	Cuseohygrine	Alkaloids
	Isopelletierine	Alkaloids
	Withaferin A	Steroidal lactones
	Sitoindosides	Acylsterylglucosides
	5-Dehydroxy withanolide-R	Steroidal lactones
	Withasomniferin-A	Steroidal lactones
Bacopa monnieri	Bacopaside III	Bascosides	Restoration of memory related disorders, restoration of nerve transmission, defensive role in schizophrenia [25]	NMDAR1 receptor turnover, stimulates certain kinases activity essential for normal neural transmission activity [26]
	Bacopaside X	Bascosides
	Bacoside A3	Bascosides
	Bacopasaponin C	Bascosides
	Apigenin	Flavonoid
	Jujubogerin	Saponin glycosides
	Pseudojujubogenin	Saponin glycosides
	Cucurbitacin	Tetracyclic terpenes
	Hersaponin	Alkaloids
	Brahmine	Alkaloids
	Monnierasides I–III	Phenylethanoid glycosides
	D-Mannitol	Sugar alcohol
	Nicotine	Alkaloids
	Herpestine	Glycoside
	Ebelin lactone	Lactone
Centella asiatica	Eugenol derivatives	Phenylpropanoid derivatives	Enhances cognition, improves memory. Anxiyolytic, anticonvulsant, protects against beta amyloid toxicity [27]	Improves antioxidative signaling pathways like Nrf2 and HO-1 pathways Impacts other signal transduction pathways like ERK1/2 and PKB pathway [27]
	Flavonoids	Phenylpropanoid derivatives
	Caffeoylquinic acids	Phenylpropanoid derivatives
	Plant sterols	Isoprenoids
	Sesquiterpenes	Isoprenoids
	Pentacyclic triterpenoids	Isoprenoids
	Saponins	Glycoside compounds

NMDAR1: N-methyl-D-aspartate receptor 1; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase-1; ERK1/2: extracellular signal-regulated protein kinases 1 and 2; PKB: protein kinase B

Declarations

Author contributions

SG: Writing—original draft, Investigation. PSS: Writing—review & editing, Investigation. DG: Conceptualization, Writing—original draft, Writing—review & editing, Investigation.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Ghosh D, Firdaus SB, Mitra E, Dey M, Bandyopadhyay D. Protective effect of aqueous leaf extract of Murraya Koenigi against lead induced oxidative stress in rat liver, heart and kidney: a dose response study. Asian J Pharm Clin Res. 2012;5:54–8.

Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015;33:1582–614. [DOI] [PubMed] [PMC]

Ghosh D, Parida P. Drugs from the Ocean: a review. World J Pharm Pharm Sci. 2014;3:1437–42.

Kinghorn AD, Pan L, Fletcher JN, Chai H. The relevance of higher plants in lead compound discovery programs. J Nat Prod. 2011;74:1539–55. [DOI] [PubMed] [PMC]

Ghosh D, Mitra E, Firdaus SB, Dey M, Ghosh AK, Chattopadhyay A, et al. In vitro studies on the antioxidant potential of the aqueous extract of Curry leaves (Murraya koenigii L.) collected from different parts of the state of West Bengal. Ind J Physiol Allied Sci. 2012;66:77–95.

Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 2013;1830:3670–95. [DOI] [PubMed] [PMC]

Ghosh D, Firdaus SB, Mitra E, Chattopadhyay A, Pattari SK, Dutta S, et al. Aqueous leaf extract of Murraya koenigii protects against lead-induced cardio toxicity in male wistar rats. Int J Phytopharm. 2013;4:119–32.

Mahleyuddin NN, Moshawih S, Ming LC, Zulkifly HH, Kifli N, Loy MJ, et al. Coriandrum sativum L.: a review on ethnopharmacology, phytochemistry, and cardiovascular benefits. Molecules. 2021;27:209. [DOI] [PubMed] [PMC]

Milla PG, Peñalver R, Nieto G. Health benefits of uses and applications of Moringa oleifera in bakery products. Plants (Basel). 2021;10:318. [DOI] [PubMed] [PMC]

10.

Mitra E, Ghosh D, Ghosh AK, Basu A, Chattopadhyay A, Pattari SK, et al. Aqueous Tulsi leaf (Ocimum sanctum) extract possesses antioxidant properties and protects against cadmium-induced oxidative stress in rat heart. Int J Pharm Pharm Sci. 2014;6:500–13.

11.

Paul S, Ghosh AK, Ghosh D, Dutta D, Mitra E, Dey M, et al. Aqueous bark extract of Terminalia arjuna protects against phenylhydrazine induced oxidative damage in goat red blood cell membrane protein, phospholipid asymmetry and structural morphology: a flow cytometric and biochemical analysis. J Pharm Res. 2014;8:1790–804.

12.

Gong X, Sucher NJ. Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development. Trends Pharmacol Sci. 1999;20:191–6. [DOI] [PubMed]

13.

Elufioye TO, Berida TI, Habtemariam S. Plants-derived neuroprotective agents: cutting the cycle of cell death through multiple mechanisms. Evid Based Complement Alternat Med. 2017;2017:3574012. [DOI] [PubMed] [PMC]

14.

Iriti M, Vitalini S, Fico G, Faoro F. Neuroprotective herbs and foods from different traditional medicines and diets. Molecules. 2010;15:3517–55. [DOI] [PubMed] [PMC]

15.

Kumar GP, Khanum F. Neuroprotective potential of phytochemicals. Pharmacogn Rev. 2012;6:81–90. [DOI] [PubMed] [PMC]

16.

Kumar V. Potential medicinal plants for CNS disorders: an overview. Phytother Res. 2006;20:1023–35. [DOI] [PubMed]

17.

Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8:208–13. [DOI] [PubMed] [PMC]

18.

Sharma CG. Ashwagandharishta--rastantra sar evam sidhyaprayog sangrah--krishna--gopal ayurveda bhawan (dharmarth trust). Nagpur; 1938. pp. 743–4.

19.

Yin H, Cho DH, Park SJ, Han SK. GABA-mimetic actions of Withania somnifera on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. Am J Chin Med. 2013;41:1043–51. [DOI] [PubMed]

20.

Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7:463–9. [DOI] [PubMed]

21.

Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5:334–46. [PubMed]

22.

Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res. 1987;1:32–7. [DOI]

23.

Atta-ur-Rahman, Abbas S, Dur-e-Shahwar, Jamal SA, Choudhary MI. New withanolides from Withania sp. J Nat Prod. 1993;56:1000–6. [DOI]

24.

Dar NJ, MuzamilAhmad. Neurodegenerative diseases and Withania somnifera (L.): an update. J Ethnopharmacol. 2020;256:112769. [DOI] [PubMed]

25.

Sekhar VC, Viswanathan G, Baby S. Insights into the molecular aspects of neuroprotective bacoside A and Bacopaside I. Curr Neuropharmacol. 2019;17:438–46. [DOI] [PubMed] [PMC]

26.

Hiren Kumar Bose. Medicinal herb ushers prosperity for Sagar Island farmers [Internet]. Village Square; 2023 [cited 2023 Oct 26]. Available from: https://www.villagesquare.in/medicinal-herb-ushers-prosperity-for-sagar-island-farmers/

27.

Newall CA, Anderson LA, Phillipson JD. Herbal medicines. A guide for health care professionals. London: The Pharmaceutical Press; 1996.

28.

Mathur D, Goyal K, Koul V, Anand A. The molecular links of re-emerging therapy: a review of evidence of Brahmi (Bacopa monniera). Front Pharmacol. 2016;7:44. [DOI] [PubMed] [PMC]

29.

Singh H, Dhawan B. Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn. (Brahmi). Ind J Pharmacol. 1997;29:359.

30.

Piyabhan P, Wetchateng T. Neuroprotective effects of Bacopa monnieri (Brahmi) on novel object recognition and NMDAR1 immunodensity in the prefrontal cortex, striatum and hippocampus of sub-chronic phencyclidine rat model of schizophrenia. J Med Assoc Thai. 2014;97:S50–5. [PubMed]

31.

Khan MB, Ahmad M, Ahmad S, Ishrat T, Vaibhav K, Khuwaja G, et al. Bacopa monniera ameliorates cognitive impairment and neurodegeneration induced by intracerebroventricular-streptozotocin in rat: behavioral, biochemical, immunohistochemical and histopathological evidences. Metab Brain Dis. 2015;30:115–27. [DOI] [PubMed]

32.

Rajan KE, Singh HK, Parkavi A, Charles PD. Attenuation of 1-(m-chlorophenyl)-biguanide induced hippocampus-dependent memory impairment by a standardised extract of Bacopa monniera (BESEB CDRI-08). Neurochem Res. 2011;36:2136–44. [DOI] [PubMed]

33.

Singh R, Ramakrishna R, Bhateria M, Bhatta RS. In vitro evaluation of Bacopa monniera extract and individual constituents on human recombinant monoamine oxidase enzymes. Phytother Res. 2014;28:1419–22. [DOI] [PubMed]

34.

Singh RH, Singh L. Studies on the anti-anxiety effect of the medhya rasayana drug brahmi (Bacopa moniera Wettst), part I. J Res Ayur Siddha. 1981;1:133–48.

35.

Peth-Nui T, Wattanathorn J, Muchimapura S, Tong-Un T, Piyavhatkul N, Rangseekajee P, et al. Effects of 12-week Bacopa monnieri consumption on attention, cognitive processing, working memory, and functions of both cholinergic and monoaminergic systems in healthy elderly volunteers. Evid Based Complement Alternat Med. 2012;2012:606424. [DOI] [PubMed] [PMC]

36.

Rauf K, Subhan F, Al-Othman A, Khan I, Zarrelli A, Shah MR. Preclinical profile of bacopasides from Bacopa monnieri (BM) as an emerging class of therapeutics for management of chronic pains. Curr Med Chem. 2013;20:1028–37. [DOI]

37.

Kapoor R, Srivastava S, Kakkar P. Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environ Toxicol Pharmacol. 2009;27:62–9. [DOI] [PubMed]

38.

Blázquez-Sánchez MT, de Matos AM, Rauter AP. Exploring anti-prion glyco-based and aromatic scaffolds: a chemical strategy for the quality of life. Molecules. 2017;22:864. [DOI] [PubMed] [PMC]

39.

Holcomb LA, Dhanasekaran M, Hitt AR, Young KA, Riggs M, Manyam BV. Bacopa monniera extract reduces amyloid levels in PSAPP mice. J Alzheimers Dis. 2006;9:243–51. [DOI] [PubMed]

40.

Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol. 2008;120:112–7. [DOI] [PubMed]

41.

Anand T, Prakash KB, Pandareesh MD, Khanum F. Development of bacoside enriched date syrup juice and its evaluation for physical endurance. J Food Sci Technol. 2014;51:4026–32. [DOI] [PubMed] [PMC]

42.

Deepak M, Amit A. The need for establishing identities of ‘bacoside A and B’, the putative major bioactive saponins of Indian medicinal plant Bacopa monnieri. Phytomedicine. 2004;11:264–8. [DOI] [PubMed]

43.

Chakravarty AK, Sarkar T, Masuda K, Shiojima K, Nakane T, Kawahara N. Bacopaside I and II: two pseudojujubogenin glycosides from Bacopa monniera. Phytochemistry. 2001;58:553–6. Erratum in: Phytochemistry. 2002;59:365. [DOI] [PubMed]

44.

Pardridge WM. Blood-brain barrier biology and methodology. J Neurovirol. 1999;5:556–69. [DOI] [PubMed]

45.

De K, Chandra S, Misra M. Evaluation of the biological effect of brahmi (Bacopa monnieri Linn) extract on the biodistribution of technetium-99m radiopharmaceuticals. Life Sci J. 2008;5:45–9.

46.

Ahmad F, Abiha U, Ahmad SR, Patel N. Ebelin lactone as the most promising neuroprotective compound from Bacopa monnieri extract targeting microtubule affinity regulation kinase-4 involved in Alzheimer’s disease: a computational study. Research Square [Preprint]. 2023 [cited 2023 Dec 15]. Available from: https://www.researchsquare.com/article/rs-2879310/v1

47.

Singh B, Pandey S, Rumman M, Kumar S, Kushwaha PP, Verma R, et al. Neuroprotective and neurorescue mode of action of Bacopa monnieri (L.) Wettst in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease: an in silico and in vivo study. Front Pharmacol. 2021;12:616413. [DOI] [PubMed] [PMC]

48.

Mondal B, Khatua DC. White rot of Centella asiatica and two weeds in West Bengal, India. J Crop and Weed. 2015;11:225–6.

49.

Gray NE, Alcazar Magana A, Lak P, Wright KM, Quinn J, Stevens JF, et al. Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochem Rev. 2018;17:161–94. [DOI] [PubMed] [PMC]

50.

Kapoor LD. Handbook of Ayurvedic medicinal plants. 1st Edition. Boca Raton: CRC Press; 1990.

51.

Shinomol GK, Muralidhara MMB. Exploring the role of “Brahmi” (Bacopa monnieri and Centella asiatica) in brain function and therapy. Recent Pat Endocr Metab Immune Drug Discov. 2011;5:33–49. [DOI]

52.

Nadkarni KM. Indian materia medica. In: Popular Prakashan. Bombay; 1976. p. 1142.

53.

Cichon N, Saluk-Bijak J, Gorniak L, Przyslo L, Bijak M. Flavonoids as a natural enhancer of neuroplasticity—an overview of the mechanism of neurorestorative action. Antioxidants (Basel). 2020;9:1035. [DOI] [PubMed] [PMC]

54.

Bandopadhyay S, Mandal S, Ghorai M, Jha NK, Kumar M, Radhaet al. Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: a review. J Cell Mol Med. 2023;27:593–608. [DOI] [PubMed] [PMC]

55.

Matthews DG, Caruso M, Murchison CF, Zhu JY, Wright KM, Harris CJ, et al. Centella Asiatica improves memory and promotes antioxidative signaling in 5XFAD mice. Antioxidants (Basel). 2019;8:630. [DOI] [PubMed] [PMC]

56.

Dar PA, Singh LR, Kamal MA, Dar TA. Unique medicinal properties of Withania somnifera: phytochemical constituents and protein component. Curr Pharm Des. 2016;22:535–40. [DOI] [PubMed]

57.

Saleem S, Muhammad G, Hussain MA, Altaf M, Bukhari SNA. Withania somnifera L.: insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iran J Basic Med Sci. 2020;23:1501–26. [DOI] [PubMed] [PMC]

58.

Umadevi M, Rajeswari R, Rahale CS, Selvavenkadesh S, Pushpa R, Kumar KPS, et al. Traditional and medicinal uses of Withania somnifera. Pharma Innovation. 2012;1:102–10.

59.

Walker EA, Pellegrini MV. Bacopa monnieri. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. [PubMed]

60.

Mathew J, Gangadharan G, Kuruvilla KP, Paulose CS. Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri. Neurochem Res. 2011;36:7–16. [DOI] [PubMed]

61.

Sairam K, Dorababu M, Goel RK, Bhattacharya SK. Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Phytomedicine. 2002;9:207–11. [DOI] [PubMed]

62.

Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine. 2005;12:305–17. [DOI] [PubMed]

63.

Ghosh TR, Maity TK, Das M, Bose A, Dash DK. In vitro antioxidant and hepatoprotective activity of ethanolic extract of Bacopa monnieri Linn. aerial parts. IJPT. 2007;6:77–85.

64.

Elangovan V, Govindasamy S, Ramamoorthy N, Balasubramanian K. In vitro studies on the anticancer activity of Bacopa monnieri. Fitoterapia. 1995;66:211–5.

65.

Jain P, Khanna NK, Trehan N, Pendse VK, Godhwani JL. Antiinflammatory effects of an Ayurvedic preparation, Brahmi Rasayan, in rodents. Indian J Exp Biol. 1994;32:633–6. [PubMed]

66.

Abbas M, Subhan F, Mohani N, Rauf K, Ali G, Khan M. The involvement of opioidergic mechanisms in theactivity of Bacopa monnieri extract and its toxicological studies. Afr J Pharm Pharmacol. 2011;5:1120–4.

67.

Bhattacharya SK, Ghosal S. Anxiolytic activity of a standardized extract of Bacopa monniera: an experimental study. Phytomedicine. 1998;5:77–82. [DOI] [PubMed]

68.

Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res. 2002;16:639–45. [DOI] [PubMed]

69.

Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol. 1999;65:1–11. [DOI] [PubMed]

70.

Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. 2013;16:313–26. [DOI] [PubMed] [PMC]

71.

Mato L, Wattanathorn J, Muchimapura S, Tongun T, Piyawatkul N, Yimtae K, et al. Centella asiatica improves physical performance and health-related quality of life in healthy elderly volunteer. Evid Based Complement Alternat Med. 2011;2011:579467. [DOI] [PubMed] [PMC]

72.

Wu F, Bian D, Xia Y, Gong Z, Tan Q, Chen J, et al. Identification of major active ingredients responsible for burn wound healing of Centella asiatica herbs. Evid Based Complement Alternat Med. 2012;2012:848093. [DOI] [PubMed] [PMC]

73.

Hengjumrut P, Anukunwithaya T, Tantisira MH, Tantisira B, Khemawoot P. Comparative pharmacokinetics between madecassoside and asiaticoside presented in a standardised extract of Centella asiatica, ECa 233 and their respective pure compound given separately in rats. Xenobiotica. 2018;48:18–27. [DOI] [PubMed]

74.

Gohil KJ, Patel JA, Gajjar AK. Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci. 2010;72:546–56. [DOI] [PubMed] [PMC]

75.

Somchit MN, Sulaiman MR, Zuraini A, Samsuddin L, Somchit N, Israf DA, et al. Antinociceptive and antiinflammatory effects of Centella asiatica. Indian J Pharmacol. 2004;36:377–80.

76.

Babu TD, Kuttan G, Padikkala J. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) Urban. J Ethnopharmacol. 1995;48:53–7. [DOI] [PubMed]