Exploration of Neuroscience

Table 2. Clinical studies supporting the neuroprotective applications of triterpenoids

SN	Triterpenoid under study	Year	Condition	Type	Subjects	Duration	Findings	Ref
1	Ginsenoside Rd	2009	Acute ischemic stroke	Randomized, double-blind, placebo-controlled, phase 2, multicenter trial	199	14 days	Improvement in NIHSS score	[94] Clinical trial ID NCT00591084
2	Ginsenoside Rd	2012	Acute ischemic stroke	Randomized, double-blind, placebo-controlled, phase 3, multicenter trial	390	14 days	Improvement in primary outcome of acute ischaemic stroke Acceptable adverse-event profile	[93] Clinical trial ID NCT00815763
3	Centella asiatica selected triterpenes (CAST)	2022	Diabetic neuropathy	Randomized, double-blind, placebo-controlled, phase 2, trial	43	52 weeks	Reduced severity of symptoms	[96] Clinical trial ID NCT00608439
4	Licorice whole extract	2016	Acute ischemic stroke	Randomized, double-blind, placebo-controlled, phase 2, trial	75	7 days	Improvement in NIHSS score	[95] Clinical trial ID NCT02473458
5	Bacopa monnieri extract	2017	Healthy	Randomized, double-blind, placebo-controlled, phase 1, trial	75	16 weeks	NA	Clinical trial ID NCT02931747
6	Bacopa monnieri extract	2007	Schizophrenia	Randomized, open label, phase 2, trial	200	4 weeks	NA	Clinical trial ID NCT00483964

Return to article view

SN: serial number; NIHSS: National Institute of Health stroke scale; NA: not available

Declarations

Acknowledgments

Ms. Apoorva A. Bankar would like to acknowledge University Grants Commission (UGC), New Delhi for providing fellowship for doctoral studies.

Author contributions

AAB: Investigation, Writing—original draft, Writing—review & editing. VPN: Conceptualization, Writing—review & editing. NRK: Conceptualization, Supervision, Validation. NNI: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

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

Mony TJ, Elahi F, Choi JW, Park SJ. Neuropharmacological Effects of Terpenoids on Preclinical Animal Models of Psychiatric Disorders: A Review. Antioxidants. Antioxidants (Basel). 2022;11:1834. [DOI] [PubMed] [PMC]

Volcho KP, Laev SS, Ashraf GM, Aliev G, Salakhutdinov NF. Application of Monoterpenoids and their Derivatives for Treatment of Neurodegenerative Disorders. Curr Med Chem. 2019;25:5327–46. [DOI] [PubMed]

Islam MT, da Silva CB, de Alencar MV, Paz MF, Almeida FR, Melo-Cavalcante AA. Diterpenes: Advances in Neurobiological Drug Research. Phytotherapy Research. 2016;30:915–28. [DOI] [PubMed]

Moujir L, Callies O, Sousa PMC, Sharopov F, Seca AML. Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases. Appl Sci. 2020;10:3001. [DOI]

Ruszkowski P, Bobkiewicz-Kozlowska T. Natural Triterpenoids and their Derivatives with Pharmacological Activity Against Neurodegenerative Disorders. Mini Rev Org Chem. 2014;11:307–15. [DOI]

Sun A, Xu X, Lin J, Cui X, Xu R. Neuroprotection by Saponins. Phytotherapy Research. 2015;29:187–200. [DOI] [PubMed]

Hill RA, Connolly JD. Triterpenoids. Nat Prod Rep. 2018;35:1294–329. [DOI]

Hill RA, Connolly JD. Triterpenoids. Nat Prod Rep. 2013;30:1028–65. [DOI]

Welbat J, Chaisawang P, Pannangrong W, Wigmore P. Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in the Hippocampus in an Adult Rat Model. Nutrients. 2018;10:1053. [DOI] [PubMed] [PMC]

10.

Loganathan C, Thayumanavan P. Asiatic acid prevents the quinolinic acid-induced oxidative stress and cognitive impairment. Metab Brain Dis. 2018;33:151–59. [DOI] [PubMed]

11.

Chaisawang P, Sirichoat A, Chaijaroonkhanarak W, Pannangrong W, Sripanidkulchai B, Wigmore P, et al. Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy. PLoS One. 2017;12:e0180650. [DOI] [PubMed] [PMC]

12.

Umka Welbat J, Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Pakdeechote P, et al. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival. Nutrients. 2016;8:303. [DOI] [PubMed] [PMC]

13.

Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Leksomboon R, Chaichun A, et al. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus. Nutrients. 2015;7:8413–23. [DOI] [PubMed] [PMC]

14.

Xu M, Xiong Y, Liu J, Qian J, Zhu L, Gao J. Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharmacol Sin. 2012;33:578–87. [DOI] [PubMed] [PMC]

15.

Park JH, Seo YH, Jang JH, Jeong CH, Lee S, Park B. Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway. J Neuroinflammation. 2017;14:240. [DOI] [PubMed] [PMC]

16.

Qian Y, Xin Z, Lv Y, Wang Z, Zuo L, Huang X, et al. Asiatic acid suppresses neuroinflammation in BV2 microglia via modulation of the Sirt1/NF-κB signaling pathway. Food Funct. 2018;9:1048–57. [DOI] [PubMed]

17.

Ding L, Liu T, Ma J. Neuroprotective mechanisms of Asiatic acid. Heliyon. 2023;9:e15853. [DOI] [PubMed] [PMC]

18.

Wong JH, Barron AM, Abdullah JM. Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease. Front Pharmacol. 2021;12:687935. [DOI] [PubMed] [PMC]

19.

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]

20.

Orhan IE. Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential. Evid Based Complement Alternat Med. 2012;2012:1–8. [DOI] [PubMed] [PMC]

21.

Cheng W, Chen W, Wang P, Chu J. Asiatic acid protects differentiated PC12 cells from Aβ_25–35-induced apoptosis and tau hyperphosphorylation via regulating PI3K/Akt/GSK-3β signaling. Life Sci. 2018;208:96–101. [DOI] [PubMed]

22.

Zhang X, Wu J, Dou Y, Xia B, Rong W, Rimbach G, et al. Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis. Eur J Pharmacol. 2012;679:51–59. [DOI] [PubMed]

23.

Ahmad Rather M, Justin-Thenmozhi A, Manivasagam T, Saravanababu C, Guillemin GJ, Essa MM. Asiatic Acid Attenuated Aluminum Chloride-Induced Tau Pathology, Oxidative Stress and Apoptosis Via AKT/GSK-3β Signaling Pathway in Wistar Rats. Neurotox Res. 2019;35:955–68. [DOI] [PubMed]

24.

Ahmad Rather M, Justin Thenmozhi A, Manivasagam T, Dhivya Bharathi M, Essa MM, Guillemin GJ. Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer’s disease. Front Biosci (Schol Ed). 2018;10:262–75. [DOI] [PubMed]

25.

Chen D, Zhang XY, Sun J, Cong QJ, Chen WX, Ahsan HM, et al. Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial ROS Production. Biomol Ther (Seoul). 2019;27:442–9. [DOI] [PubMed] [PMC]

26.

Ding H, Xiong Y, Sun J, Chen C, Gao J, Xu H. Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria. Front Neurosci. 2018;12:431. [DOI] [PubMed] [PMC]

27.

Chao PC, Lee HL, Yin MC. Asiatic acid attenuated apoptotic and inflammatory stress in the striatum of MPTP-treated mice. Food Funct. 2016;7:1999–2005. [DOI] [PubMed]

28.

Nataraj J, Manivasagam T, Justin Thenmozhi A, Essa MM. Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells. Nutr Neurosci. 2017;20:351–9. [DOI] [PubMed]

29.

Wang Z, Mong M, Yang Y, Yin M. Asiatic acid and maslinic acid attenuated kainic acid-induced seizure through decreasing hippocampal inflammatory and oxidative stress. Epilepsy Res. 2018;139:28–34. [DOI] [PubMed]

30.

Lu CW, Lin TY, Pan TL, Wang PW, Chiu KM, Lee MY, et al. Asiatic Acid Prevents Cognitive Deficits by Inhibiting Calpain Activation and Preserving Synaptic and Mitochondrial Function in Rats with Kainic Acid-Induced Seizure. Biomedicines. 2021;9:284. [DOI] [PubMed] [PMC]

31.

Wang Y, Wang H, Zhao P, Cheng J, Gong W, Zhang J. Asiatic acid exerts neuroprotective effect against hypoxicischemic brain injury in neonatal rats via inhibition of oxidative damage. Trop J Pharm Res. 2021;20:1903–8. [DOI]

32.

Lee KY, Bae ON, Weinstock S, Kassab M, Majid A. Neuroprotective Effect of Asiatic Acid in Rat Model of Focal Embolic Stroke. Biol Pharm Bull. 2014;37:1397–401. [DOI] [PubMed]

33.

Lee KY, Bae ON, Serfozo K, Hejabian S, Moussa A, Reeves M, et al. Asiatic Acid Attenuates Infarct Volume, Mitochondrial Dysfunction, and Matrix Metalloproteinase-9 Induction After Focal Cerebral Ischemia. Stroke. 2012;43:1632–8. [DOI] [PubMed] [PMC]

34.

Krishnamurthy RG, Senut M, Zemke D, Min J, Frenkel MB, Greenberg EJ, et al. Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia. J Neurosci Res. 2009;87:2541–50. [DOI] [PubMed] [PMC]

35.

Gurcan O, Gurcay AG, Kazanci A, Senturk S, Bodur E, Umay Karaca E, et al. Effect of Asiatic Acid on the Treatment of Spinal Cord Injury: An Experimental Study in Rats. Turk Neurosurg. 2015;27:259–64. [DOI] [PubMed]

36.

Jiang W, Li M, He F, Bian Z, He Q, Wang X, et al. Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci. 2016;157:45–51. [DOI] [PubMed]

37.

Han F, Yan N, Huo J, Chen X, Fei Z, Li X. Asiatic acid attenuates traumatic brain injury via upregulating Nrf2 and HO-1 expression. Int J Clin Exp Med. 2018;11:360–6.

38.

Chen T, Giri M, Xia Z, Subedi YN, Li Y. Genetic and epigenetic mechanisms of epilepsy: a review. Neuropsychiatr Dis Treat. 2017;13:1841–59. [DOI] [PubMed] [PMC]

39.

Surguchov A, Surgucheva I, Sharma M, Sharma R, Singh V. Pore-Forming Proteins as Mediators of Novel Epigenetic Mechanism of Epilepsy. Front Neurol. 2017;8:3. [DOI] [PubMed] [PMC]

40.

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

41.

He Z, Hu Y, Niu Z, Zhong K, Liu T, Yang M, et al. A review of pharmacokinetic and pharmacological properties of asiaticoside, a major active constituent of Centella asiatica (L.) Urb. J Ethnopharmacol. 2023;302:115865. [DOI] [PubMed]

42.

Zhang Z, Li X, Li D, Luo M, Li Y, Song L, et al. Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors. Exp Ther Med. 2017;13:413–20. [DOI] [PubMed] [PMC]

43.

Song D, Jiang X, Liu Y, Sun Y, Cao S, Zhang Z. Asiaticoside Attenuates Cell Growth Inhibition and Apoptosis Induced by Aβ1-42 via Inhibiting the TLR4/NF-κB Signaling Pathway in Human Brain Microvascular Endothelial Cells. Front Pharmacol. 2018;9:28. [DOI] [PubMed] [PMC]

44.

Liu S, Chen L, Li J, Sun Y, Xu Y, Li Z, et al. Asiaticoside Mitigates Alzheimer’s Disease Pathology by Attenuating Inflammation and Enhancing Synaptic Function. Int J Mol Sci. 2023;24:11976. [DOI] [PubMed] [PMC]

45.

Xu CL, Wang QZ, Sun LM, Li XM, Deng JM, Li LF, et al. Asiaticoside: Attenuation of neurotoxicity induced by MPTP in a rat model of Parkinsonism via maintaining redox balance and up-regulating the ratio of Bcl-2/Bax. Pharmacol Biochem Behav. 2012;100:413–18. [DOI] [PubMed]

46.

Gopi M, Arambakkam Janardhanam V. Asiaticoside: Attenuation of rotenone induced oxidative burden in a rat model of hemiparkinsonism by maintaining the phosphoinositide-mediated synaptic integrity. Pharmacol Biochem Behav. 2017;155:1–15. [DOI] [PubMed]

47.

Sampath U, Janardhanam VA. Asiaticoside, a trisaccaride triterpene induces biochemical and molecular variations in brain of mice with parkinsonism. Transl Neurodegener. 2013;2:23. [DOI] [PubMed] [PMC]

48.

Chen S, Yin ZJ, Jiang C, Ma ZQ, Fu Q, Qu R, et al. Asiaticoside attenuates memory impairment induced by transient cerebral ischemia–reperfusion in mice through anti-inflammatory mechanism. Pharmacol Biochem Behav. 2014;122:7–15. [DOI] [PubMed]

49.

Sun T, Liu B, Li P. Nerve Protective Effect of Asiaticoside against Ischemia-Hypoxia in Cultured Rat Cortex Neurons. Med Sci Monit. 2015; 21:3036–41. [DOI] [PubMed] [PMC]

50.

Zhou Y, Wang S, Zhao J, Fang P. Asiaticoside attenuates neonatal hypoxic–ischemic brain damage through inhibiting TLR4/NF-κB/STAT3 pathway. Ann Transl Med. 2020;8:641. [DOI] [PubMed] [PMC]

51.

Luo Y, Fu C, Wang Z, Zhang Z, Wang H, Liu Y, et al. Asiaticoside attenuates the effects of spinal cord injury through antioxidant and anti-inflammatory effects, and inhibition of the p38-MAPK mechanism. Mol Med Rep. 2015;12:8294–300. [DOI] [PubMed]

52.

Fan L, Li X, Liu T. Asiaticoside Inhibits Neuronal Apoptosis and Promotes Functional Recovery After Spinal Cord Injury in Rats. J Mol Neurosci. 2020;70:1988–96. [DOI] [PubMed]

53.

Hu Z, Wu T, Zhou Z, Zhang Y, Chen Q, Yao H, et al. Asiaticoside Attenuates Blood–Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury. Mol Neurobiol. 2024;61:678–92. [DOI] [PubMed]

54.

Wang L, Guo T, Guo Y, Xu Y. Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway. Mol Med Rep. 2020;22:2364–72. [DOI] [PubMed] [PMC]

55.

Mamun A, Katakura M, Matsuzaki K, Hossain S, Arai H, Shido O. Neuroprotective Effect of Madecassoside Evaluated Using Amyloid β1-42-Mediated in Vitro and in Vivo Alzheimer’s Disease Models. Int J Indig. 2014;47:1669–82.

56.

Du B, Zhang Z, Li N. Madecassoside prevents Aβ25–35-induced inflammatory responses and autophagy in neuronal cells through the class III PI3K/Beclin-1/Bcl-2 pathway. Int Immunopharmacol. 2014;20:221–8. [DOI] [PubMed]

57.

Lin X, Zhang S, Huang R, Wei L, Tan S, Liang C, et al. Protective effect of madecassoside against cognitive impairment induced by d-galactose in mice. Pharmacol Biochem Behav. 2014;124:434–42. [DOI] [PubMed]

58.

Ling Z, Zhou S, Zhou Y, Zhong W, Su Z, Qin Z. Protective role of madecassoside from Centella asiatica against protein L-isoaspartyl methyltransferase deficiency-induced neurodegeneration. Neuropharmacology. 2024;246:109834. [DOI] [PubMed]

59.

Xu CL, Qu R, Zhang J, Li LF, Ma SP. Neuroprotective effects of madecassoside in early stage of Parkinson’s disease induced by MPTP in rats. Fitoterapia. 2013;90:112–8. [DOI] [PubMed]

60.

Luo Y, Wang C, Li WH, Liu J, He HH, Long JH, et al. Madecassoside protects BV2 microglial cells from oxygen-glucose deprivation/reperfusion-induced injury via inhibition of the toll-like receptor 4 signaling pathway. Brain Res. 2018;1679:144–54. [DOI] [PubMed]

61.

Li SQ, Xie YS, Meng QW, Zhang J, Zhang T. Neuroprotective properties of Madecassoside from Centella asiatica after hypoxic-ischemic injury. Pak J Pharm Sci. 2016;29:2047–51. [PubMed]

62.

Luo Y, Yang YP, Liu J, Li WH, Yang J, et al. Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats. Brain Res. 2014;1565:37–47. [DOI] [PubMed]

63.

Kunjumon R, Viswanathan G, Jayasree DV, Biju PG, Prakash P, Sasidharan BCP, et al. Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure. Phytomedicine Plus. 2021;1:100004. [DOI]

64.

Liu S, Li G, Tang H, Pan R, Wang H, Jin F, et al. Madecassoside ameliorates lipopolysaccharide-induced neurotoxicity in rats by activating the Nrf2-HO-1 pathway. Neurosci Lett. 2019;709:134386. [DOI] [PubMed]

65.

Sasmita AO, Ling APK, Voon KGL, Koh RY, Wong YP. Madecassoside activates anti-neuroinflammatory mechanisms by inhibiting lipopolysaccharide induced microglial inflammation. Int J Mol Med. 2018;41:3033–40. [DOI] [PubMed]

66.

Sivaramakrishna C, Rao CV, Trimurtulu G, Vanisree M, Subbaraju GV. Triterpenoid glycosides from Bacopa monnieri. Phytochemistry. 2005;66:2719–28. [DOI] [PubMed]

67.

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]

68.

Nandy S, Dey A, Mukherjeeb A. Advances in dammarane-type triterpenoid saponins from Bacopa monnieri: Structure, bioactivity, biotechnology and neuroprotection. In: Atta-ur-Rahman., editor. Studies in Natural Products Chemistry. Elsevier; 2019. pp. 489–533.

69.

Bhardwaj P, Jain CK, Mathur A. Comparative evaluation of four triterpenoid glycoside saponins of bacoside A in alleviating sub-cellular oxidative stress of N2a neuroblastoma cells. J Pharm Pharmacol. 2018;70:1531–40. [DOI] [PubMed]

70.

Ghosh A, Khanam N, Nath D. Evaluation on antioxidative and neuroprotective activity of bacoside- A, Asiatic acid and kaempferol in endothelin-1 induced cerebral ischemia in rat. J Appl Pharm Sci. 2023;13:223–31. [DOI]

71.

Anbarasi K, Vani G, Balakrishna K, Devi CSS. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sci. 2006;78:1378–84. [DOI] [PubMed]

72.

Bist R, Chaudhary B, Bhatt DK. Defensive proclivity of bacoside A and bromelain against oxidative stress and AChE gene expression induced by dichlorvos in the brain of Mus musculus. Sci Rep. 2021;11:3668. [DOI] [PubMed] [PMC]

73.

Madhu K, Prakash T, Prakash T. Bacoside-A inhibits inflammatory cytokines and chemokine in experimental autoimmune encephalomyelitis. Biomed Pharmacother. 2019;109:1339–45. [DOI] [PubMed]

74.

Zhang B, Shi J, Chang L, Wang H, Wang Y, Li M, et al. Bacoside-A exerts protective effect against Parkinson’s disease-induced functional damage in mice via inhibition of apoptosis and oxidative response. Trop J Pharm Res. 2021;19:2565–70. [DOI]

75.

Bai QK, Zhao ZG. Isolation and neuronal apoptosis inhibitory property of bacoside-A3 via downregulation of β-amyloid induced inflammatory response. Biotechnol Appl Biochem. 2022;69:726–34. [DOI] [PubMed]

76.

Mathew J, Peeyush Kumar T, Khan RS, Paulose CS. Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: Effect of Bacopa monnieri and bacoside A. Epilepsy Behav. 2010;17:441–7. [DOI] [PubMed]

77.

Sekhar VC, 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. 2023;61:3296–313. [DOI] [PubMed]

78.

Singh B, Pandey S, Rumman M, Gupta M, Mahdi AA. Bacopaside-I ameliorates motor dysfunction and neurodegeneration in rat model of Parkinson’s disease. [Preprint]. 2022 [cited 2024 April 20]. Available from: https://www.researchsquare.com/article/rs-1983926/v1

79.

Liu X, Yue R, Zhang J, Shan L, Wang R, Zhang W. Neuroprotective effects of bacopaside I in ischemic brain injury. Restor Neurol Neurosci. 2013;31:109–23. [DOI] [PubMed]

80.

Luz DA, Pinheiro AM, Fontes-Júnior EA, Maia CSF. Neuroprotective, neurogenic, and anticholinergic evidence of Ganoderma lucidum cognitive effects: Crucial knowledge is still lacking. Med Res Rev. 2023;43:1504–36. [DOI] [PubMed]

81.

Cui J, Meng YH, Wang ZW, Wang J, Shi DF, Liu D. Ganoderic Acids A and B Reduce Okadaic Acid-Induced Neurotoxicity in PC12 Cells by Inhibiting Tau Hyperphosphorylation. Biomed Environ Sci. 2023;36:103–8. [DOI] [PubMed]

82.

Zhang Y, Wang X, Yang X, Yang X, Xue J, Yang Y. Ganoderic Acid A To Alleviate Neuroinflammation of Alzheimer’s Disease in Mice by Regulating the Imbalance of the Th17/Tregs Axis. J Agric Food Chem. 2021;69:14204–14. [DOI] [PubMed]

83.

Qi LF, Liu S, Liu YC, Li P, Xu X. Ganoderic Acid A Promotes Amyloid-β Clearance (In Vitro) and Ameliorates Cognitive Deficiency in Alzheimer’s Disease (Mouse Model) through Autophagy Induced by Activating Axl. Int J Mol Sci. 2021;22:5559. [DOI] [PubMed] [PMC]

84.

Li QM, Wu SZ, Zha XQ, Zang DD, Zhang FY, Luo JP. Ganoderic acid A mitigates dopaminergic neuron ferroptosis via inhibiting NCOA4-mediated ferritinophagy in Parkinson’s disease mice. J Ethnopharmacol. 2024;332:118363. [DOI] [PubMed]

85.

Pang W, Lu S, Zheng R, Li X, Yang S, Feng Y, et al. Investigation into Antiepileptic Effect of Ganoderic Acid A and Its Mechanism in Seizure Rats Induced by Pentylenetetrazole. Biomed Res Int. 2022;2022:5940372. [DOI] [PubMed] [PMC]

86.

Yang ZW, Wu F, Zhang SL. Effects of ganoderic acids on epileptiform discharge hippocampal neurons: insights from alterations of BDNF,TRPC3 and apoptosis. Pharmazie. 2016;71:340–4. [PubMed]

87.

Abulizi A, Ran J, Ye Y, An Y, Zhang Y, Huang Z, et al. Ganoderic acid improves 5-fluorouracil-induced cognitive dysfunction in mice. Food Funct. 2021;12:12325–37. [DOI] [PubMed]

88.

Zheng C, Rangsinth P, Shiu PHT, Wang W, Li R, Li J, et al. A Review on the Sources, Structures, and Pharmacological Activities of Lucidenic Acids. Molecules. 2023;28:1756. [DOI] [PubMed] [PMC]

89.

Cör D, Knez Ž, Knez Hrnčič M. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review. Molecules. 2018;23:649. [DOI] [PubMed] [PMC]

90.

Lee I, Ahn B, Choi J, Hattori M, Min B, Bae K. Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett. 2011; 21:6603–7. [DOI] [PubMed]

91.

Wei JC, Wang YX, Dai R, Tian XG, Sun CP, Ma XC, et al. C27-Nor lanostane triterpenoids of the fungus Ganoderma lucidum and their inhibitory effects on acetylcholinesteras. Phytochem Lett. 2017;20:263–8. [DOI]

92.

Ćilerdžić JL, Sofrenić IV, Tešević VV, Brčeski ID, Duletić-Laušević SN, Vukojević JB, et al. Neuroprotective Potential and Chemical Profile of Alternatively Cultivated Ganoderma lucidum Basidiocarps. Chem Biodivers. 2018;15:e1800036. [DOI] [PubMed]

93.

Liu X, Wang L, Wen A, Yang J, Yan Y, Song Y, et al. Ginsenoside-Rd improves outcome of acute ischaemic stroke – a randomized, double-blind, placebo-controlled, multicenter trial. Eur J Neurol. 2012;19:855–63. [DOI] [PubMed]

94.

Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y, et al. Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial. Eur J Neurol. 2009;16:569–75. [DOI] [PubMed]

95.

Ravanfar P, Namazi G, Atigh M, Zafarmand S, Hamedi A, Salehi A, et al. Efficacy of whole extract of licorice in neurological improvement of patients after acute ischemic stroke. J Herb Med. 2016;6:12–17. [DOI]

96.

Lou JS, Dimitrova DM, Murchison C, Arnold GC, Belding H, Seifer N, et al. Centella asiatica triterpenes for diabetic neuropathy: a randomized, double-blind, placebo-controlled, pilot clinical study. Esper Dermatol. 2018;20:12–22. [DOI] [PubMed] [PMC]

97.

Bai X, Fu RJ, Zhang S, Yue SJ, Chen YY, Xu DQ, et al. Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases. Biomed Pharmacothe. 2021;139:111551. [DOI] [PubMed]

98.

Graber DJ, Park PJ, Hickey WF, Harris BT. Synthetic Triterpenoid CDDO Derivatives Modulate Cytoprotective or Immunological Properties in Astrocytes, Neurons, and Microglia. J Neuroimmune Pharmacol. 2011;6:107–20. [DOI] [PubMed]

99.

Gudoityte E, Arandarcikaite O, Mazeikiene I, Bendokas V, Liobikas J. Ursolic and Oleanolic Acids: Plant Metabolites with Neuroprotective Potential. Int J Mol Sci. 2021;22:4599. [DOI] [PubMed] [PMC]