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Nutritive value and toxicity of Sauropus androgynous

Bender AE, Ismail KS

Proc Nutr Soc, 1973 Sep;32(2):79A-80A.
PMID: 4791076
Fulltext Linking Ayurveda and Western medicine by integrative analysis

Fauzi FM, Koutsoukas A, Lowe R, Joshi K, Fan TP, Glen RC, et al.

J Ayurveda Integr Med, 2013 Apr;4(2):117-9.
PMID: 23930045 DOI: 10.4103/0975-9476.113882

In this article, we discuss our recent work in elucidating the mode-of-action of compounds used in traditional medicine including Ayurvedic medicine. Using computational ('in silico') approach, we predict potential targets for Ayurvedic anti-cancer compounds, obtained from the Indian Plant Anticancer Database given its chemical structure. In our analysis, we observed that: (i) the targets predicted can be connected to cancer pathogenesis i.e. steroid-5-alpha reductase 1 and 2 and estrogen receptor-β, and (ii) predominantly hormone-dependent cancer targets were predicted for the anti-cancer compounds. Through the use of our in silico target prediction, we conclude that understanding how traditional medicine such as Ayurveda work through linking with the 'western' understanding of chemistry and protein targets can be a fruitful avenue in addition to bridging the gap between the two different schools of thinking. Given that compounds used in Ayurveda have been tested and used for thousands of years (although not in the same approach as Western medicine), they can potentially be developed into potential new drugs. Hence, to further advance the case of Ayurvedic medicine, we put forward some suggestions namely: (a) employing and integrating novel analytical methods given the advancements of 'omics' and (b) sharing experimental data and clinical results on studies done on Ayurvedic compounds in an easy and accessible way.
Understanding the mode-of-action of Cassia auriculata via in silico and in vivo studies towards validating it as a long term therapy for type II diabetes

Mohd Fauzi F, John CM, Karunanidhi A, Mussa HY, Ramasamy R, Adam A, et al.

J Ethnopharmacol, 2017 Feb 02;197:61-72.
PMID: 27452659 DOI: 10.1016/j.jep.2016.07.058

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia auriculata (CA) is used as an antidiabetic therapy in Ayurvedic and Siddha practice. This study aimed to understand the mode-of-action of CA via combined cheminformatics and in vivo biological analysis. In particular, the effect of 10 polyphenolic constituents of CA in modulating insulin and immunoprotective pathways were studied.
MATERIALS AND METHODS: In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signalling, based on a model trained on known bioactivity data and chemical similarity considerations. Next, CA was investigated in in vivo studies where induced type 2 diabetic rats were treated with CA for 28 days and the expression levels of genes regulating insulin signalling pathway, glucose transporters of hepatic (GLUT2) and muscular (GLUT4) tissue, insulin receptor substrate (IRS), phosphorylated insulin receptor (AKT), gluconeogenesis (G6PC and PCK-1), along with inflammatory mediators genes (NF-κB, IL-6, IFN-γ and TNF-α) and peroxisome proliferators-activated receptor gamma (PPAR-γ) were determined by qPCR.
RESULTS: In silico analysis shows that several of the top 20 enriched targets predicted for the constituents of CA are involved in insulin signalling pathways e.g. PTPN1, PCK-α, AKT2, PI3K-γ. Some of the predictions were supported by scientific literature such as the prediction of PI3K for epigallocatechin gallate. Based on the in silico and in vivo findings, we hypothesized that CA may enhance glucose uptake and glucose transporter expressions via the IRS signalling pathway. This is based on AKT2 and PI3K-γ being listed in the top 20 enriched targets. In vivo analysis shows significant increase in the expression of IRS, AKT, GLUT2 and GLUT4. CA may also affect the PPAR-γ signalling pathway. This is based on the CA-treated groups showing significant activation of PPAR-γ in the liver compared to control. PPAR-γ was predicted by the in silico target prediction with high normalisation rate although it was not in the top 20 most enriched targets. CA may also be involved in the gluconeogenesis and glycogenolysis in the liver based on the downregulation of G6PC and PCK-1 genes seen in CA-treated groups. In addition, CA-treated groups also showed decreased cholesterol, triglyceride, glucose, CRP and Hb1Ac levels, and increased insulin and C-peptide levels. These findings demonstrate the insulin secretagogue and sensitizer effect of CA.
CONCLUSION: Based on both an in silico and in vivo analysis, we propose here that CA mediates glucose/lipid metabolism via the PI3K signalling pathway, and influence AKT thereby causing insulin secretion and insulin sensitivity in peripheral tissues. CA enhances glucose uptake and expression of glucose transporters in particular via the upregulation of GLUT2 and GLUT4. Thus, based on its ability to modulate immunometabolic pathways, CA appears as an attractive long term therapy for T2DM even at relatively low doses.
Fulltext Establishing GPCR Targets of hMAO Active Anthraquinones from Cassia obtusifolia Linn Seeds Using In Silico and In Vitro Methods

Paudel P, Seong SH, Fauzi FM, Bender A, Jung HA, Choi JS

ACS Omega, 2020 Apr 07;5(13):7705-7715.
PMID: 32280914 DOI: 10.1021/acsomega.0c00684

The present study examines the effect of human monoamine oxidase active anthraquinones emodin, alaternin (=7-hydroxyemodin), aloe-emodin, and questin from Cassia obtusifolia Linn seeds in modulating human dopamine (hD1R, hD3R, and hD4R), serotonin (h5-HT1AR), and vasopressin (hV1AR) receptors that were predicted as prime targets from proteocheminformatics modeling via in vitro cell-based functional assays, and explores the possible mechanisms of action via in silico modeling. Emodin and alaternin showed a concentration-dependent agonist effect on hD3R with EC50 values of 21.85 ± 2.66 and 56.85 ± 4.59 μM, respectively. On hV1AR, emodin and alaternin showed an antagonist effect with IC50 values of 10.25 ± 1.97 and 11.51 ± 1.08 μM, respectively. Interestingly, questin and aloe-emodin did not have any observable effect on hV1AR. Only alaternin was effective in antagonizing h5-HT1AR (IC50: 84.23 ± 4.12 μM). In silico studies revealed that a hydroxyl group at C1, C3, and C8 and a methyl group at C6 of anthraquinone structure are essential for hD3R agonist and hV1AR antagonist effects, as well as for the H-bond interaction of 1-OH group with Ser192 at a proximity of 2.0 Å. Thus, based on in silico and in vitro results, hV1AR, hD3R, and h5-HT1AR appear to be prime targets of the tested anthraquinones.
Fulltext Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes

Mohamad Zobir SZ, Mohd Fauzi F, Liggi S, Drakakis G, Fu X, Fan TP, et al.

Evid Based Complement Alternat Med, 2016;2016:2106465.
PMID: 26989424 DOI: 10.1155/2016/2106465

Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, "the foundation of acquired constitution" that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications.