Therapeutic potential of phytocompounds of Bacopa monnieri (L.) Wettst (literature review)

O.O. Nikitina; D.S.  Tsyba

doi:10.26641/2307-0404.2024.3.313488

Authors

O.O. Nikitina Kyiv National University of Technologies and Design, Mala Shyianovska str., 2, Kyiv, 01011, Ukraine https://orcid.org/0000-0001-6994-4294
D.S. Tsyba Kyiv National University of Technologies and Design, Mala Shyianovska str., 2, Kyiv, 01011, Ukraine https://orcid.org/0009-0001-9881-5990

DOI:

https://doi.org/10.26641/2307-0404.2024.3.313488

Keywords:

Bacopa monnieri, phytocompounds, bacosides, nootropic properties, cognitive disorders

Abstract

The aim of the work was to evaluate the pharmacological effects and therapeutic potential of individual compounds and extracts of B. monnieri based on the analysis of data from scientific periodicals regarding chemical composition and biological action. Theoretically significant were the studies of the materials of the scientific-metric database PubMed and Google Scholar over the last five years regarding the chemical composition and biological action of extracts based on B. monnieri and their individual components. The search query was carried out by the Latin name of the plant, with the exception of publications related to botanical research. In separate PubChem searches, names of individual phytocompounds were used to establish structure and distribution in plants. The SuperPred web server was used to predict therapeutic potential. The authors analyzed the chemical composition of the extracts, presented the structural and pharmacological characteristics of bacosides and their aglycones: bacosin and juubogenin, cucurbitacin E, loliolide, betulinic and asiatic acids and the flavonoid oroxindin. The mechanism of action of bacoside on β-amyloid is characterized and illustrated. Using machine learning, the prospects for using the main compounds of bacopa to create drugs were calculated taking into account the ATC classification, their biological effects and alternative plant sources were given. Experimental animal studies of whole aqueous or ethanolic extracts of B. monnieri have been found to support a cognitive enhancement effect. The extract was not toxic to humans. Numerous clinical trials show the effectiveness of the use of extracts in the treatment of anhedonia, depression, Alzheimer's disease, Parkinson's disease, dementia and hyperactivity. An analysis of clinical studies in Ukraine shows that drugs based on B. monnieri can be used in the complex treatment of cognitive impairment associated with dyscirculatory encephalopathy in adults and perinatal CNS damage in children. Considering the amphiphilicity of bacosides and the non-toxicity of extracts, they can be involved in the development of various dosage forms with a wide range of therapeutic applications. Further study of the pharmacological action of B. monnieri and the development of drug technology for solid and liquid dosage forms based on it are promising.

References

Chaachouay N, Zidane L. Plant-Derived Natural Products: A Source for Drug Discovery and Develop-ment. Drugs Drug Candidates. 2024;3:184-207. doi: https://doi.org/10.3390/ddc3010011

Thakral S, Yadav A, Singh V, Kumar M, et al. Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs. Ageing Res Rev. 2023 Jul;88:101960. doi: https://doi.org/10.1016/j.arr.2023.101960

Nopparat J, Sujipuli K, Ratanasut K, Weerawatanakorn M, Prasarnpun S, Thongbai B, et al. Exploring the excellence of commercial Brahmi products from Thai online markets: Unraveling phytochemical contents, antioxidant properties and DNA damage protection. Heliyon. 2024;10(2):e24509. doi: https://doi.org/10.1016/j.heliyon.2024.e24509

Shalini VT, Neelakanta SJ, Sriranjini JS. Neuro-protection with Bacopa monnieri-A review of expe-rimental evidence. Mol Biol Rep. 2021;48(3):2653-68. doi: https://doi.org/10.1007/s11033-021-06236-w

Fatima U, Roy S, Ahmad S, Ali S, Elkady WM, Khan I, et al. Pharmacological attributes of Bacopa mon-nieri extract: Current updates and clinical manifestation. Front Nutr. 2022;9:972379. doi: https://doi.org/10.3389/fnut.2022.972379

Sekhar VC, Viswanathan G, Baby S. Insights Into the Molecular Aspects of Neuroprotective Bacoside A and Bacopaside I. Curr Neuropharmacol. 2019;17(5):438-46. doi: https://doi.org/10.2174/1570159X16666180419123022

Delgado-Tiburcio EE, Cadena-Iñiguez J, Santiago-Osorio E, Ruiz-Posadas LDM, Castillo-Juárez I, Aguiñiga-Sánchez I, et al. Pharmacokinetics and Biolo-gical Activity of Cucurbitacins. Pharmaceuticals (Basel). 2022;15(11):1325. doi: https://doi.org/10.3390/ph15111325

Sekhar CV, Gulia KK, Deepti A, Chakrapani PSB, Baby S, Viswanathan G. Protection by Nano-Encapsulated Bacoside A and Bacopaside I in Seizure Alleviation and Improvement in Sleep- In Vitro and In Vivo Evidences. Mol Neurobiol. 2024;61(6):3296-313. doi: https://doi.org/10.1007/s12035-023-03741-w

Bala SD, Saravanan R, Mahalakshmi G, Murali R, Ashokkumar N. Bacoside-A Improves Antioxidant Enzymes and Alleviates Oxidative Stress Coexist with Markers of Renal Function in a Rat Model of Type 2 Diabetes Mellitus. Saudi J Kidney Dis Transpl. 2023 Nov 1;34(6):537-47. doi: https://doi.org/10.4103/sjkdt.sjkdt_163_21

Nishanth BJ, Vijayababu P, Kurian NK. Bacopa monnieri Extract As a Neuroprotective and Cognitive Enhancement Agent. Int J Drug Discov Pharmacol. 2023;2(4):44-56. doi: https://doi.org/10.53941/ijddp.2023.100015

Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, Wong EH, et al. Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies. Drug Target Insights. 2019;13:1177392819866412. doi: https://doi.org/10.1177/1177392819866412

Ramesh T, Shahid M. Bacoside-A repressed the differentiation and lipid accumulation of 3T3-L1 preadipocytes by modulating the expression of adipogenic genes. Biotechnol Appl Biochem. 2024;71(1):1-239. doi: https://doi.org/10.1002/bab.2573

Rauf K, Subhan F, Sewell RD. A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover. Phytother Res. 2012;26(5):758-63. doi: https://doi.org/10.1002/ptr.3631

Ferrucci M, Busceti CL, Lazzeri G, Biagioni F, Puglisi-Allegra S, Frati A, et al. Bacopa Protects against Neurotoxicity Induced by MPP+ and Methamphetamine. Molecules. 2022;27(16):5204. doi: https://doi.org/10.3390/molecules27165204

Cheng Y, Li R, Lin Z, Chen F, Dai J, Zhu Z, et al. Structure-activity relationship analysis of dammarane-type natural products as muscle-type creatine kinase activators. Bioorg Med Chem Lett. 2020;30(17):127364. doi: https://doi.org/10.1016/j.bmcl.2020.127364

Ruan W, Liu J, Zhang S, Huang Y, Zhang Y, Wang Z. Sour Jujube (Ziziphus jujuba var. spinosa): A Bibliometric Review of Its Bioactive Profile, Health Benefits and Trends in Food and Medicine Applications. Foods. 2024;13(5):636. doi: https://doi.org/10.3390/foods13050636

Sangsopha W, Lekphrom R, Schevenels FT, Ka-nokmedhakul K, Kanokmedhakul S. Two new bioactive triterpenoids from the roots of Colubrina asiatica. Nat Prod Res. 2020;34(4):482-8. doi: https://doi.org/10.1080/14786419.2018.1489385

Huangteerakul C, Aung HM, Thosapornvichai T, Duangkaew M, Jensen AN, Sukrong S, et al. Chemical-Genetic Interactions of Bacopa monnieri Constituents in Cells Deficient for the DNA Repair Endonuclease RAD1 Appear Linked to Vacuolar Disruption. Molecules. 2021 Feb 24;26(5):1207. doi: https://doi.org/10.3390/molecules26051207

Souto EB, Dias-Ferreira J, Craveiro SA, Severino P, Sanchez-Lopez E, Garcia ML, et al. Therapeutic Interventions for Countering Leishmaniasis and Chagas's Disease: From Traditional Sources to Nanotechnological Systems. Pathogens. 2019;8(3):119. doi: https://doi.org/10.3390/pathogens8030119

Ríos JL, Máñez S. New Pharmacological Opportunities for Betulinic Acid. Planta Med. 2018;84(1):8-19. doi: https://doi.org/10.1055/s-0043-123472

Aswathy M, Vijayan A, Daimary UD, Girisa S, Radhakrishnan KV, Kunnumakkara AB. Betulinic acid: A natural promising anticancer drug, current situation, and future perspectives. J Biochem Mol Toxicol. 2022 Dec;36(12):e23206. doi: https://doi.org/10.1002/jbt.23206

Ossowicz-Rupniewska P, Klebeko J, Georgieva I, Apostolova S, Struk Ł, Todinova S, et al. Tuning of the Anti-Breast Cancer Activity of Betulinic Acid via Its Con-version to Ionic Liquids. Pharmaceutics. 2024;16(4):496. doi: https://doi.org/10.3390/pharmaceutics16040496

Sousa JLC, Freire CSR, Silvestre AJD, Silva AMS. Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds. Molecules. 2019 Jan 19;24(2):355. doi: https://doi.org/10.3390/molecules24020355

Joshi DD, Deb L, Somkuwar BG, Rana VS. Relevance of Indian traditional tisanes in the management of type 2 diabetes mellitus: A review. Saudi Pharm J. 2023 May;31(5):626-38. doi: https://doi.org/10.1016/j.jsps.2023.03.003

Yeggoni DP, Rachamallu A, Subramanyam R. Comparative binding studies of bacosine with human serum albumin and α-1-acid glycoprotein biophysical evaluation and computational approach. J Pharm Biomed Anal. 2022 Feb 5;209:114478. doi: https://doi.org/10.1016/j.jpba.2021.114478

Jeyasri R, Muthuramalingam P, Suba V, Ramesh M, Chen JT. Bacopa monnieri and Their Bioactive Compounds Inferred Multi-Target Treatment Strategy for Neurological Diseases: A Cheminformatics and System Pharmacology Approach. Biomolecules. 2020;10(4):536. doi: https://doi.org/10.3390/biom10040536

Wiciński M, Fajkiel-Madajczyk A, Kurant Z, Gajewska S, Kurant D, Kurant M, et al. Can Asiatic Acid from Centella asiatica Be a Potential Remedy in Cancer Therapy?-A Review. Cancers (Basel). 2024;16(7):1317. doi: https://doi.org/10.3390/cancers16071317

Diniz LRL, Calado LL, Duarte ABS, de Sousa DP. Centella asiatica and Its Metabolite Asiatic Acid: Wound Healing Effects and Therapeutic Potential. Metabolites. 2023;13(2):276. doi: https://doi.org/10.3390/metabo13020276

Roy S, Rakshit S, Shanmugam G, Sarkar K. Participation of Brahmi (Bacopa monnieri L.) plant in regulation of cancer. South African Journal of Botany. 2024;168:236-45. doi: https://doi.org/10.1016/j.sajb.2024.03.017

Zhan F, Song W, Fan Y, Wang F, Wang Q. Cucurbitacin E Alleviates Colonic Barrier Function Impairment and Inflammation Response and Improves Microbial Composition on Experimental Colitis Models. J Inflamm Res. 2024;17:2745-56. doi: https://doi.org/10.2147/JIR.S456353

Zheng X, Tang P, Li H, Ye T, Zhu X, He W, et al. Cucurbitacin E elicits apoptosis in laryngeal squamous cell carcinoma by enhancing reactive oxygen species-regulated mitochondrial dysfunction and endoplasmic reticulum stress. Am J Cancer Res. 2024 Aug 25;14(8):3905-21. doi: https://doi.org/10.62347/HPQQ9412

Song H, Sui H, Zhang Q, Wang P, Wang F. Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells. Front Physiol. 2020;11:1020. doi: https://doi.org/10.3389/fphys.2020.01020

Hsu HL, Lin BJ, Lin YC, Tu CC, Nguyen NL, Wang CC, et al. Cucurbitacin E Exerts Anti-Proliferative Activity via Promoting p62-Dependent Apoptosis in Human Non-Small-Cell Lung Cancer A549 Cells. Curr Issues Mol Biol. 2023;45(10):8138-51. doi: https://doi.org/10.3390/cimb45100514

Zieniuk B, Pawełkowicz M. Recent Advances in the Application of Cucurbitacins as Anticancer Agents. Metabolites. 2023;13(10):1081. doi: https://doi.org/10.3390/metabo13101081

Liu Z, Kumar M, Devi S, Kabra A. The Mechanisms of Cucurbitacin E as a Neuroprotective and Memory-Enhancing Agent in a Cerebral Hypoperfusion Rat Model: Attenuation of Oxidative Stress, Inflammation, and Excitotoxicity. Front Pharmacol. 2021 Dec 10;12:794933. doi: https://doi.org/10.3389/fphar.2021.794933

Zheng S, Shi B, Li X, Yuan H, Feng Y. Cucurbitacin E reduces the cognitive dysfunction induced by sevoflurane in rats by regulating NF-κB pathway. Acta Biochim Pol. 2022;69(2):387-91. doi: https://doi.org/10.18388/abp.2020_5817

Percot A, Yalcin A, Aysel V, Erduğan H, Dural B, Güven KC. Loliolide in marine algae. Nat Prod Res. 2009;23(5):460-5. doi: https://doi.org/10.1080/14786410802076069

Sunyamurthi IGNA, Jawi IM, Wijaya IN, Darmawati IAP, Suada IK, Krisnandika AAK. Phytochemical Analysis and Molecular Identification of Green Macroal-gae Caulerpa spp. from Bali, Indonesia. Molecules. 2022;27(15):4879. doi: https://doi.org/10.3390/molecules27154879

Reynolds D, Huesemann M, Edmundson S, Sims A, Hurst B, Cady S, et al. Viral inhibitors derived from macroalgae, microalgae, and cyanobacteria: A review of antiviral potential throughout pathogenesis. Algal Res. 2021;57:102331. doi: https://doi.org/10.1016/j.algal.2021.102331

Fernando IPS, Dias MKHM, Madusanka DMD, Kim HS, Han EJ, Kim MJ, et al. Effects of (-)-Loliolide against Fine Dust Preconditioned Keratinocyte Media-Induced Dermal Fibroblast Inflammation. Antioxidants (Basel). 2021;10(5):675. doi: https://doi.org/10.3390/antiox10050675

Cho DH, Yun JH, Heo J, Lee IK, Lee YJ, Bae S, et al. Identification of Loliolide with Anti-Aging Properties from Scenedesmus deserticola JD052. J Microbiol Biotechnol. 2023;33(9):1250-6. doi: https://doi.org/10.4014/jmb.2304.04044

Silva J, Alves C, Martins A, Susano P, Simões M, Guedes M, et al. Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum. Int J Mol Sci. 2021;22(4):1888. doi: https://doi.org/10.3390/ijms22041888

Harahap U, Syahputra RA, Ahmed A, Nasution A, Wisely W, Sirait ML, et al. Current insights and future perspectives of flavonoids: A promising antihypertensive approach. Phytother Res. 2024;38(6):3146-68. doi: https://doi.org/10.1002/ptr.8199

Ahmed SS, Rahman MO, Alqahtani AS, Sultana N, Almarfadi OM, Ali MA, et al. Anticancer potential of phytochemicals from Oroxylum indicum targeting Lactate Dehydrogenase A through bioinformatic approach. Toxicol Rep. 2022;10:56-75. doi: https://doi.org/10.1016/j.toxrep.2022.12.007

Mehta J, Utkarsh K, Fuloria S, Singh T, Sekar M, Salaria D, et al. Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uro¬pathogens-An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections. Molecules. 2022;27(15):4971. doi: https://doi.org/10.3390/molecules27154971

Geetha PS, Kanchana S, Pasupathi E, Murugan M, Rohini C. A review on putative mechanism of action of nootropic herb Bacopa monnieri. Pharma Innovation. 2021;10(5):672-81.

Nikitina OO, Robak AYu, Tsyba DS. [Innovative approaches to the use of medicinal plants in modern pharmaceuticals]. Tekhnolohii ta inzhynirynh. 2024;2:110-26. Ukrainian. doi: https://doi.org/10.30857/2786-5371.2024.3.9

Muchhara J, Vachhani K, Dave S, Patel R, Lavle N, Kukadia D, et al. Safety evaluation of the geno-toxicity and subchronic toxicity of standardized Bacopa extract (Bacognize®) from Bacopa monnieri. Toxicology Research and Application. 2023;7:23978473231162859. doi: https://doi.org/10.1177/23978473231162859

Valotto Neto LJ, Reverete de Araujo M, Moretti Junior RC, Mendes Machado N, Joshi RK, Dos Santos Buglio D, et al. Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis. Antioxidants (Basel). 2024;13(4):393. doi: https://doi.org/10.3390/antiox13040393

Slobodin T. Comprehensive metabolic correction in cognitive impairment: theoretical background for using citicoline and Bacopa monnieri combination. International neurological journal. 2021;16(7):48-54. doi: https://doi.org/10.22141/2224-0713.16.7.2020.218247

Mishchenko TS, Sokolik VV, Mishchenko VM, et al. [New opportunities in the treatment of patients with dyscirculatory encephalopathy: emphasis on nerve growth factor]. Psykhiatriia, nevrolohiia ta medychna psykholohiia. 2020;13:79-88. doi: https://doi.org/10.26565/2312-5675-2020-13-11

Sukhonosova OYu, Koreniev SM, Prykhodko TM, et al. [Optimizing the correction of sleep, speech and cognitive development disorders in children due to perinatal damage to the central nervous system]. Psykhiatriia, nevrolohiia ta medychna psykholohiia. 2020;15:64-72. doi: https://doi.org/10.26565/2312-5675-2020-15-07

SuperPred, which is a prediction webserver for ATC code and target predicition of compounds [Internet]. SuperPred. 2024 Jul 22 [cited 2024 Apr 22 ]. Available from: https://prediction.charite.de/