Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC₅₀ of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC₅₀ values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.

Background: Despite the fact that natives of Southeast Asia have been consuming Prismatomeris glabra for decades for a variety of health benefits, research on this species is not as extensive as that on other species due to its limited distribution. The purpose of this study was to determine the cytotoxicity and identify the bioactive compounds of P. glabra crude leaf extracts against the MCF-7 cell line. Results: We first examined the potential cytotoxic activity of P. glabra using the MTT assay against the MCF-7 cell line to determine the IC₅₀ of the plant extracts at various concentrations at three time points (24 h, 48 h, and 72 h). Across all time points, the MTT assay revealed that the aqueous extract exhibited the lowest IC₅₀ values (p < 0.05) compared to the ethanol and methanol extracts. All plant extracts exerted the ability to induce cell death in the MCF-7 cell line at all time points, and the optimal time for P. glabra to manifest its antiproliferative activities and promote cell death was 48 h. LC–MS analysis was conducted to reveal the components in plant extracts. Forty compounds were discovered in P. glabra's extracts, with the majority being flavonoids and triterpenoids. Five similar compounds were present in all three extracts. Further research should be conducted on these compounds to unveil a compound that fulfils the criteria as a promising anticancer agent. This research is of the utmost importance, as it provides a fundamental framework for the identification of alternative therapies for breast cancer and contributes implicitly to the development of new drugs. Conclusions: This study discovered that P. glabra crude leaf extracts have the potential to inhibit the MCF-7 cell line by inducing cell death.

Oxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow (n = 6 per group) or with a high-fat diet (HFD) for 6 weeks to induce obesity (n = 12 per group). Obese rats were further subjected to treatment either with distilled water (OB group) or orlistat 10 mg/kg/day (OB + OR group). Key indices of oxidative stress, inflammation, and apoptosis were assessed using an immunohistochemical-based technique and real-time PCR. The OB group showed significant increases of oxidative stress markers (TBARs and PCO), with significant decreases of anti-oxidant markers (Nrf2, SOD, CAT, and GPx). Furthermore, mRNA expression of pro-inflammatory markers (TNF-α and NF-κβ) and pro-apoptosis markers (Bax, Caspase-3, Caspase-8, and Caspase-9) were significantly upregulated in the OB group. Obese rats developed pathological changes of myocardial damages as evidenced by the presence of myocardial hypertrophy and inflammatory cells infiltration. Orlistat dampened the progression of myocardial damage in obese rats by ameliorating the oxidative stress, and by inhibiting NF-κβ pathway and caspase-dependent cell apoptosis. Our study proposed that orlistat could potentially mitigate oxidative stress-linked myocardial damage by mitigating inflammation and apoptosis, thus rationalizing its medical usage.

Hypoxia has been associated with cognitive impairment. Many studies have investigated the role of mTOR signalling pathway in cognitive functions but its role in hypoxia-induced cognitive impairment remains controversial. This review aimed to elucidate the role of mTOR in the mechanisms of cognitive impairment that may pave the way towards the mechanistic understanding and therapeutic intervention of hypoxia-induced cognitive impairment. mTORC1 is normally regulated during mild or acute hypoxic exposure giving rise to neuroprotection, whereas it is overactivated during severe or chronic hypoxia giving rise to neuronal cells death. Thus, it is worth exploring the possibility of maintaining normal mTORC1 activity and thereby preventing cognitive impairment during severe or chronic hypoxia.

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy characterised by the accumulation of monoclonal mature B lymphocytes (positive for CD5+ and CD23+) in peripheral blood, bone marrow, and lymph nodes. Although CLL is reported to be rare in Asian countries compared to Western countries, the disease course is more aggressive in Asian countries than in their Western counterparts. It has been postulated that this is due to genetic variants between populations. Various cytogenomic methods, either of the traditional type (conventional cytogenetics or fluorescence in situ hybridisation (FISH)) or using more advanced technology such as DNA microarrays, next generation sequencing (NGS), or genome wide association studies (GWAS), were used to detect chromosomal aberrations in CLL. Up until now, conventional cytogenetic analysis remained the gold standard in diagnosing chromosomal abnormality in haematological malignancy including CLL, even though it is tedious and time-consuming. In concordance with technological advancement, DNA microarrays are gaining popularity among clinicians as they are faster and better able to accurately diagnose the presence of chromosomal abnormalities. However, every technology has challenges to overcome. In this review, CLL and its genetic abnormalities will be discussed, as well as the application of microarray technology as a diagnostic platform.

Centella asiatica (L.) Urban (C. asiatica) is a medicinal plant that generates terpenes, phenols, vitamins, minerals, polyacetylene and fatty acids among other phyto-constituents. This review focuses on the bibliometric analysis of 1164 documents on C. asiatica that were retrieved from the Scopus database. Harzing Publish or Perish and VOSviewer were used for citation and network analyses. According to the bibliometric analysis, publications are on the rise, particularly in the fields of pharmacology, toxicology and pharmaceutics, medicine, biochemistry, genetics and molecular biology, agricultural and biological sciences, and chemistry. "Phytoremediation", "secondary metabolites", "Andrographis paniculata", and "cognitive impairment" are emerging areas for C. asiatica research. However, currently there is a lack of international collaboration in C. asiatica research among contributing countries. Researchers can utilise the findings cited in this reiew to locate potential collaborators, top authors, countries and documents.