The Pentacyclic Triterpenoids in Herbal Medicines and Their Pharmacological Activities in Diabetes and Diabetic Complications

Alqahtani, Ali S.; Hamid, Kaiser; Kam, Antony; Wong, K. C.; Abdelhak, Z; Razmovski-Naumovski, Valentina; Chan, Kelvin; Li, Kong M.; Groundwater, Paul W.; Li, George Q.

doi:10.2174/092986713805219082

Cited by 99 publications

(89 citation statements)

References 209 publications

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“…The n-hexane fraction of Myagropsis myagroides showed significant amylase inhibition [32]. Saleh et al (2013) observed significant α-glucosidase and α-amylase inhibitory in the n-hexane fractions of ten plant extracts traditionally used in Iran for diabetes [33,34].…”

Section: α-Amylase and α-Glucosidase Inhibition Studiesmentioning

confidence: 99%

Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia

et al. 2019

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Nuxia oppositifolia is traditionally used in diabetes treatment in many Arabian countries; however, scientific evidence is lacking. Hence, the present study explored the antidiabetic and antioxidant activities of the plant extracts and their purified compounds. The methanolic crude extract of N. oppositifolia was partitioned using a two-solvent system. The n-hexane fraction was purified by silica gel column chromatography to yield several compounds including katononic acid and 3-oxolupenal. Antidiabetic activities were assessed by α-amylase and α-glucosidase enzyme inhibition. Antioxidant capacities were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging assays. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (3-oxolupenal and katononic acid) was followed by fluorescence quenching and molecular docking studies. 3-oxolupenal and katononic acid showed IC50 values of 46.2 μg/mL (101.6 µM) and 52.4 μg/mL (119.3 µM), respectively against the amylase inhibition. 3-oxolupenal (62.3 µg/mL or 141.9 μM) exhibited more potent inhibition against α-glucosidases compared to katononic acid (88.6 µg/mL or 194.8 μM). In terms of antioxidant activity, the relatively polar crude extract and n-butanol fraction showed the greatest DPPH and ABTS scavenging activity. However, the antioxidant activities of the purified compounds were in the low to moderate range. Molecular docking studies confirmed that 3-oxolupenal and katononic acid interacted strongly with the active site residues of both α-amylase and α-glucosidase. Fluorescence quenching results also suggest that 3-oxolupenal and katononic acid have a good affinity towards both α-amylase and α-glucosidase enzymes. This study provides preliminary data for the plant’s use in the treatment of type 2 diabetes mellitus.

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Section: α-Amylase and α-Glucosidase Inhibition Studiesmentioning

confidence: 99%

Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia

et al. 2019

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“…UA has been shown to exert many beneficial effects such as anti-diabetes [36], anti-obesity [37], and anti-cancer [38]. Several recent studies show that UA exerts its anti-tumor role through inhibition of the mTOR signaling pathway [39], suggesting a potential mechanism underlying the beneficial effects of UA.…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Inhibits Leucine-Stimulated mTORC1 Signaling by Suppressing mTOR Localization to Lysosome

Liu

Luo

et al. 2014

PLoS ONE

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Ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, has been reported to possess a wide range of beneficial properties including anti-hyperglycemia, anti-obesity, and anti-cancer. However, the molecular mechanisms underlying the action of UA remain largely unknown. Here we show that UA inhibits leucine-induced activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway in C2C12 myotubes. The UA-mediated inhibition of mTORC1 is independent of Akt, tuberous sclerosis complex 1/2 (TSC1/2), and Ras homolog enriched in brain (Rheb), suggesting that UA negatively regulates mTORC1 signaling by targeting at a site downstream of these mTOR regulators. UA treatment had no effect on the interaction between mTOR and its activator Raptor or inhibitor Deptor, but suppressed the binding of RagB to Raptor and inhibited leucine-induced mTOR lysosomal localization. Taken together, our study identifies UA as a direct negative regulator of the mTORC1 signaling pathway and suggests a novel mechanism by which UA exerts its beneficial function.

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“…Betulinic acid, a pentacyclic triterpenoid, is widely found in the medicinal plants (Gauthier et al, 2011), including Bacopa monniera Diospyros bipindensis (Viji et al, 2010), (Brusotti et al, 2017), (James and Dubery, Centella asiatica 2009), (Qian et al, 2012) etc. Betulinic acid Zizyphi spinosi was reported to have a wide spectrum of pharmacological activities such as, antioxidant (Yamashita et al, 2002), antiinflammatory (Viji et al, 2010), antimalarial (de Sá et al, 2009, antidiabetic (Alqahtani et al, 2013), antidepressant (Machado et al, 2013), anti-HIV (Fujioka et al, 1994), antihepatitis C (Lin et al, 2015), antineoplasic (Fulda, 2009) and immunomodulatory activities (Pang et al, 2018). In addition, betulin or its bioactive derivative betulinic acid showed neuroprotective effects in cerebral ischemiareperfusion injury (Lu et al, 2011), Parkinson's disease (Tsai et al, 2017), epilepsy (Muceniece et al, 2008), amyloid beta-induced neurotoxicity (Planchard et al,2012) and multiple sclerosis (Blazevski et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Ameliorative effect of Betulinic acid on ageing and scopolamine-induced learning and memory impairment in rats

Ruhal¹,

Dhingra²

2018

Asian J Pharm Pharmacol

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Background: Ageing is a natural process which includes a progressive decline in cognitive functions as a result of maladaptation of cholinergic neuronal activity. The reason behind ageing-induced cholinergic neuronal loss is largely unknown, however, oxidative stress is speculated to be majorly involved in its aetiology. In the present Objectives: study, the effect of betulinic acid was evaluated on learning and memory in aged rats as well as scopolamine-induced amnesic rats. Betulinic acid (25 and 50 mg/kg; p.o.) was administered to separate groups of Material and methods: rats for 7consecutive days. Donepezil (1 mg/kg; i.p.), an acetylcholinesterase inhibitor was used as a standard drug. Behavioral models such as Morris water maze and elevated plus maze were used to evaluate the effect of drugs on learning and memory of rats. After behavioral studies, animals were sacrificed and their brain was isolated and further processed for estimation of various biochemical parameters such as acetylcholinesterase activity, oxidative and nitrosative stress markers and histological examinations. Betulinic acid significantly improved learning and Results: memory of aged as well as scopolamine-induced amnesic rats. Further, betulinic acid significantly reduced oxidativenitrosative stress, as indicated by decreased lipid peroxidation and nitrite level and increased the levels of reduced glutathione and superoxide dismutase, in both aged as well as scopolamine-induced amnesic rats. Further, the AChEs activity was found to be significantly reduced after administration of high dose (50 mg/kg) of betulinic acid in aged rats as well as scopolamine-induced amnesic rats. In addition, histopathological evaluation showed that betulinic acidtreated aged rats have less number of pyknotic neurons in hippocampal CA1 region as compared to aged control rats. Conclusion: The present study provides the pharmacological evidence for neuroprotective and memory enhancing effect of betulinic acid in aged as well as scopolamine-induced amnesic rats, possibly through its antiacetylcholinesterase activity and anti-oxidant activity. Further, the current findings support the usefulness of betulinic acid in the management of age-related cognitive dysfunction.

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The Pentacyclic Triterpenoids in Herbal Medicines and Their Pharmacological Activities in Diabetes and Diabetic Complications

Cited by 99 publications

References 209 publications

Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia

Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia

Ursolic Acid Inhibits Leucine-Stimulated mTORC1 Signaling by Suppressing mTOR Localization to Lysosome

Ameliorative effect of Betulinic acid on ageing and scopolamine-induced learning and memory impairment in rats

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