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  1. Fulltext In silico and in vitro studies of lupeol and iso-orientin as potential antidiabetic agents in a rat model
    Malik A, Jamil U, Butt TT, Waquar S, Gan SH, Shafique H, et al.
    Drug Des Devel Ther, 2019;13:1501-1513.
    PMID: 31123393 DOI: 10.2147/DDDT.S176698
    Background: In silico characterization can help to explain the interaction between molecules and predict three-dimensional structures. Various studies have confirmed the glucose-lowering effects of plant extracts, ie, lupeol and iso-orientin, which enable them to be used as antidiabetic agents. Purpose: Aims of the present study were to evaluate the hypoglycemic activities of lupeol and iso-orientin in a rat model. The study proposed the effects of alloxan on blood glucose level, body weight, and oxidative stress. Materials and Methods: Thirty (n=30) Wistar albino rats were divided into six groups and were subjected to different combinations of the compounds. Levels of different stress markers, ie, malondialdehyde, superoxide dismutase, catalase, nitric oxide, glutathione, glutathione peroxide, glutathione reductase, and blood glucose levels were estimated with their respective methods. Whereas, for their in silico analysis, identified target proteins, GPR40, glucose-6-phosphatase, UCP2, glycogen phosphorylase, aldose reductase, and glucose transporter-4 were docked with lupeol and iso-orientin. Three-dimensional structures were predicted by ERRAT, Rampage, Verify3D, threading and homology approaches. Results: Blood glucose levels were significantly increased in rats receiving intraperitoneal injection of alloxan (208±6.94 mg/dL) as compared to controls (90±7.38 mg/dL). Infected rats were administered plant extracts; combined treatment of both extracts (lupeol+iso-orientin) significantly reduced the levels of blood glucose (129.06±6.29 mg/dL) and improved the antioxidant status. Fifteen structures of each selected protein were evaluated using various techniques. Consequently, satisfactory quality factors [GPR40 (96.41%), glucose-6-phosphatase (96.56%), UCP2 (72.56%), glycogen phosphorylase (87.24%), aldose reductase (82.46%), and glucose transporter-4 (94.29%)] were selected. Molecular docking revealed interacting residues, effective drug properties and their binding affinities (ie, -8.9 to -12.6 Kcal/mol). Conclusion: Results of the study affirmed the antidiabetic activities of lupeol and iso-orientin. Administration of these extracts (either individually or in combination) significantly reduced blood glucose levels and oxidative stress. Hence, it may be considered beneficial in the treatment of diabetes.
    Matched MeSH terms: Pentacyclic Triterpenes/therapeutic use*
  2. Fulltext The centella asiatica juice effects on DNA damage, apoptosis and gene expression in hepatocellular carcinoma (HCC)
    Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A
    BMC Complement Altern Med, 2014 Jan 20;14:32.
    PMID: 24444147 DOI: 10.1186/1472-6882-14-32
    BACKGROUND: This paper is to investigate the effects of Centella asiatica on HepG2 (human hepatocellular liver carcinoma cell line). Centella asiatica is native to the Southeast Asia that is used as a traditional medicine. This study aims to determine the chemopreventive effects of the Centella asiatica juice on human HepG2 cell line.

    METHODS: Different methods including flow cytometry, comet assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to show the effects of juice exposure on the level of DNA damage and the reduction of cancerous cells. MTT assay is a colorimetric method applied to measure the toxic effects of juice on cells.

    RESULTS: The Centella asiatica juice was not toxic to normal cells. It showed cytotoxic effects on tumor cells in a dose dependent manner. Apoptosis in cells was started after being exposed for 72 hr of dose dependent. It was found that the higher percentage of apoptotic cell death and DNA damage was at the concentration above 0.1%. In addition, the juice exposure caused the reduction of c-myc gene expression and the enhancement of c-fos and c-erbB2 gene expressions in tumor cells.

    CONCLUSIONS: It was concluded that the Centella asiatica juice reduced liver tumor cells. Thus, it has the potential to be used as a chemopreventive agent to prevent and treat liver cancer.

    Matched MeSH terms: Triterpenes/therapeutic use*
  3. Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae)
    Sabandar CW, Jalil J, Ahmat N, Aladdin NA
    Phytochemistry, 2017 Feb;134:6-25.
    PMID: 27889244 DOI: 10.1016/j.phytochem.2016.11.010
    The genus Dillenia is comprised of about 100 species of evergreen and deciduous trees or shrubs of disjunct distribution in the seasonal tropics of Madagascar through South and South East Asia, Malaysia, North Australia, and Fiji. Species from this genus have been widely used in medicinal folklore to treat cancers, wounds, jaundice, fever, cough, diabetes mellitus, and diarrhea as well as hair tonics. The plants of the genus also produce edible fruits and are cultivated as ornamental plants. Flavonoids, triterpenoids, and miscellaneous compounds have been identified in the genus. Their extracts and pure compounds have been reported for their antimicrobial, anti-inflammatory, cytotoxic, antidiabetes, antioxidant, antidiarrheal, and antiprotozoal activities. Mucilage from their fruits is used in drug formulations.
    Matched MeSH terms: Triterpenes/therapeutic use
  4. Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids
    Coldren CD, Hashim P, Ali JM, Oh SK, Sinskey AJ, Rha C
    Planta Med, 2003 Aug;69(8):725-32.
    PMID: 14531023
    The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella's bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.
    Matched MeSH terms: Triterpenes/therapeutic use
  5. Aqueous extract of Centella asiatica promotes corneal epithelium wound healing in vitro
    Ruszymah BH, Chowdhury SR, Manan NA, Fong OS, Adenan MI, Saim AB
    J Ethnopharmacol, 2012 Mar 27;140(2):333-8.
    PMID: 22301444 DOI: 10.1016/j.jep.2012.01.023
    Centella asiatica is a traditional herbal medicine that has been shown to have pharmacological effect on skin wound healing, and could be potential therapeutic agent for corneal epithelial wound healing.
    Matched MeSH terms: Triterpenes/therapeutic use
  6. Fulltext Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches
    Chiroma SM, Hidayat Baharuldin MT, Mat Taib CN, Amom Z, Jagadeesan S, Adenan MI, et al.
    Biomed Pharmacother, 2019 Jan;109:853-864.
    PMID: 30551539 DOI: 10.1016/j.biopha.2018.10.111
    BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats.

    MATERIALS AND METHODS: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl's staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes.

    RESULTS: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil.

    CONCLUSION: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.

    Matched MeSH terms: Triterpenes/therapeutic use*
  7. Fulltext Molecular modulators of celastrol as the keystones for its diverse pharmacological activities
    Ng SW, Chan Y, Chellappan DK, Madheswaran T, Zeeshan F, Chan YL, et al.
    Biomed Pharmacother, 2019 Jan;109:1785-1792.
    PMID: 30551432 DOI: 10.1016/j.biopha.2018.11.051
    In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
    Matched MeSH terms: Triterpenes/therapeutic use*
  8. Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells
    Jafari SF, Khadeer Ahamed MB, Iqbal MA, Al Suede FS, Khalid SH, Haque RA, et al.
    J Pharm Pharmacol, 2014 Oct;66(10):1394-409.
    PMID: 25039905 DOI: 10.1111/jphp.12272
    Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells.
    Matched MeSH terms: Triterpenes/therapeutic use*
  9. Fulltext In Silico and In Vitro Analysis of Bacoside A Aglycones and Its Derivatives as the Constituents Responsible for the Cognitive Effects of Bacopa monnieri
    Ramasamy S, Chin SP, Sukumaran SD, Buckle MJ, Kiew LV, Chung LY
    PLoS One, 2015;10(5):e0126565.
    PMID: 25965066 DOI: 10.1371/journal.pone.0126565
    Bacopa monnieri has been used in Ayurvedic medicine to improve memory and cognition. The active constituent responsible for its pharmacological effects is bacoside A, a mixture of dammarane-type triterpenoid saponins containing sugar chains linked to a steroid aglycone skeleton. Triterpenoid saponins have been reported to be transformed in vivo to metabolites that give better biological activity and pharmacokinetic characteristics. Thus, the activities of the parent compounds (bacosides), aglycones (jujubogenin and pseudojujubogenin) and their derivatives (ebelin lactone and bacogenin A1) were compared using a combination of in silico and in vitro screening methods. The compounds were docked into 5-HT1A, 5-HT2A, D1, D2, M1 receptors and acetylcholinesterase (AChE) using AutoDock and their central nervous system (CNS) drug-like properties were determined using Discovery Studio molecular properties and ADMET descriptors. The compounds were screened in vitro using radioligand receptor binding and AChE inhibition assays. In silico studies showed that the parent bacosides were not able to dock into the chosen CNS targets and had poor molecular properties as a CNS drug. In contrast, the aglycones and their derivatives showed better binding affinity and good CNS drug-like properties, were well absorbed through the intestines and had good blood brain barrier (BBB) penetration. Among the compounds tested in vitro, ebelin lactone showed binding affinity towards M1 (Ki = 0.45 μM) and 5-HT2A (4.21 μM) receptors. Bacoside A and bacopaside X (9.06 μM) showed binding affinity towards the D1 receptor. None of the compounds showed any inhibitory activity against AChE. Since the stimulation of M1 and 5-HT2A receptors has been implicated in memory and cognition and ebelin lactone was shown to have the strongest binding energy, highest BBB penetration and binding affinity towards M1 and 5-HT2A receptors, we suggest that B. monnieri constituents may be transformed in vivo to the active form before exerting their pharmacological activity.
    Matched MeSH terms: Triterpenes/therapeutic use
  10. Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme inhibition
    Abdelwahab SI, Hassan LE, Sirat HM, Yagi SM, Koko WS, Mohan S, et al.
    Fitoterapia, 2011 Dec;82(8):1190-7.
    PMID: 21871542 DOI: 10.1016/j.fitote.2011.08.002
    The in vivo and in vitro mechanistic anti-inflammatory actions of cucurbitacin E (CE) (Citrullus lanatus var. citroides) were examined. The results showed that LPS/INF-γ increased NO production in RAW264.7 macrophages, whereas L-NAME and CE curtailed it. CE did not reveal any cytotoxicity on RAW264.7 and WRL-68 cells. CE inhibited both COX enzymes with more selectivity toward COX-2. Intraperitoneal injection of CE significantly suppressed carrageenan-induced rat's paw edema. ORAC and FRAP assays showed that CE is not a potent ROS scavenger. It could be concluded that CE is potentially useful in treating inflammation through the inhibition of COX and RNS but not ROS.
    Matched MeSH terms: Triterpenes/therapeutic use*
  11. Celastrol attenuates mitochondrial dysfunction and inflammation in palmitate-mediated insulin resistance in C3A hepatocytes
    Abu Bakar MH, Sarmidi MR, Tan JS, Mohamad Rosdi MN
    Eur J Pharmacol, 2017 Mar 15;799:73-83.
    PMID: 28161417 DOI: 10.1016/j.ejphar.2017.01.043
    Accumulating evidence indicates that mitochondrial dysfunction-induced inflammation is among the convergence points for the greatest hallmarks of hepatic insulin resistance. Celastrol, an anti-inflammatory compound from the root of Tripterygium Wilfordii has been reported to mitigate insulin resistance and inflammation in animal disease models. Nevertheless, the specific mechanistic actions of celastrol in modulating such improvements at the cellular level remain obscure. The present study sought to explore the mechanistic roles of celastrol upon insulin resistance induced by palmitate in C3A human hepatocytes. The hepatocytes exposed to palmitate (0.75mM) for 48h exhibited reduced both basal and insulin-stimulated glucose uptake, mitochondrial dysfunction, leading to increased mitochondrial oxidative stress with diminished fatty acid oxidation. Elevated expressions of nuclear factor-kappa B p65 (NF-κB p65), c-Jun NH(2)-terminal kinase (JNK) signaling pathways and the amplified release of pro-inflammatory cytokines including IL-8, IL-6, TNF-α and CRP were observed following palmitate treatment. Consistently, palmitate reduced and augmented phosphorylated Tyrosine-612 and Serine-307 of insulin receptor substrate-1 (IRS-1) proteins, respectively in hepatocytes. However, celastrol at the optimum concentration of 30nM was able to reverse these deleterious occasions and protected the cells from mitochondrial dysfunction and insulin resistance. Importantly, we presented evidence for the first time that celastrol efficiently prevented palmitate-induced insulin resistance in hepatocytes at least, via improved mitochondrial functions and insulin signaling pathways. In summary, the present investigation underlines a conceivable mechanism to elucidate the cytoprotective potential of celastrol in attenuating mitochondrial dysfunction and inflammation against the development of hepatic insulin resistance.
    Matched MeSH terms: Triterpenes/therapeutic use
  12. Fulltext Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer's Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus
    Chiroma SM, Baharuldin MTH, Mat Taib CN, Amom Z, Jagadeesan S, Ilham Adenan M, et al.
    Int J Mol Sci, 2019 Apr 16;20(8).
    PMID: 31014012 DOI: 10.3390/ijms20081871
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat's hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.
    Matched MeSH terms: Triterpenes/therapeutic use
  13. Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis
    Jia H, Liu M, Wang X, Jiang Q, Wang S, Santhanam RK, et al.
    Pharmacol Res, 2021 Jul;169:105686.
    PMID: 34022397 DOI: 10.1016/j.phrs.2021.105686
    Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC.
    Matched MeSH terms: Triterpenes/therapeutic use
  14. Fulltext The hexane fraction of Ardisia crispa Thunb. A. DC. roots inhibits inflammation-induced angiogenesis
    Hamsin DE, Hamid RA, Yazan LS, Taib CN, Ting YL
    BMC Complement Altern Med, 2013;13:5.
    PMID: 23298265 DOI: 10.1186/1472-6882-13-5
    Ardisia crispa (Myrsinaceae) is used in traditional Malay medicine to treat various ailments associated with inflammation, including rheumatism. The plant's hexane fraction was previously shown to inhibit several diseases associated with inflammation. As there is a strong correlation between inflammation and angiogenesis, we conducted the present study to investigate the anti-angiogenic effects of the plant's roots in animal models of inflammation-induced angiogenesis.
    Matched MeSH terms: Triterpenes/therapeutic use
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