Muhammad Farrukh Nisar’s research while affiliated with Cholistan University of Veterinary & Animal Sciences and other places

Cancer remains a global health challenge, with drug resistance and disease recurrence posing significant obstacles despite advances in immunotherapy and targeted treatments. This has driven interest in natural products as sources of novel anticancer agents. Withania somnifera (Ashwagandha), a well-regarded plant in Ayurvedic medicine, is noted for its various therapeutic properties, including anticancer effects. Among its bioactive compounds, Withaferin A (WFA), a steroidal lactone, has shown notable promise in reducing inflammation, angiogenesis, and tumor proliferation with minimal toxicity. This review examines the anticancer properties of WFA, with a focus on its mechanisms of action, therapeutic efficacy, and safety profile across various cancer types. A comprehensive literature review was conducted, compiling data from in vitro and in vivo studies that investigate WFA’s impact on cancer hallmarks, including apoptosis induction, angiogenesis reduction, and metastasis inhibition. Key molecular interactions with NFκB, STAT, HSP90, estrogen receptors, p53, and TGFβ pathways are highlighted. Findings indicate that WFA exhibits significant anticancer activity by modulating critical signaling pathways and inducing apoptosis with minimal adverse effects. In preclinical models, WFA demonstrated therapeutic potential across multiple cancers, such as breast, colon, prostate, ovarian, lung, and brain cancers. WFA represents a promising candidate for future cancer therapies, particularly as a natural adjuvant that could enhance treatment efficacy with low toxicity. Further clinical trials are needed to explore WFA’s full potential and confirm its safety in human oncology.

Diabetes mellitus (DM), a major global health concern, is a chronic metabolic disorder. Bioactive compounds sourced from numerous marine natural products recently have drawn attention as novel therapeutic approaches. Considering these chemicals and their role in cellular redox modulation by involving the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, the current study attempts to highlight their anti-diabetic effects and the molecular mechanisms involved. Reactive oxygen species (ROS)-mediated oxidative stress, inflammation, and cellular damage are linked to most human pathologies specifically DM. The Nrf2/HO-1 pathway is a key defense mechanism developed by the cells to combat ROS burst. Marine natural compounds have strong pharmacological potential in triggering cellular antioxidant defense mechanisms by declining oxidative damage and inflammation linked to DM. How marine natural products potentially alleviate DM specifically type 2 diabetes (T2D) and its related issues is especially focused on. The literature was thoroughly analyzed to open a discussion about specific marine compounds and their well-established anti-diabetic effects to elucidate possible therapeutic applications. Furthermore, opportunities and the pros and cons of using these marine bioactive compounds as complementary treatment for DM are also discussed. The diverse characteristics of marine natural products, specifically with regard to redox control, offer promising opportunities for drug discovery and therapeutic interventions in clinical trials.

A malignant tumor is a frequent and common disease that severely threatens human health. Many mechanisms, such as cell signaling pathway, anti-apoptosis mechanism, cell stemness, metabolism, and cell phenotype, have been studied to explain the reasons for chemotherapy, radioresistance, and tumor recurrences in antitumor treatment. Cancer stem cells (CSCs) are important tumor cell subclasses that can potentially organize and regulate stem cell properties. Growing evidence suggests that CSCs can initiate tumors and constitute a significant factor in metastasis, recurrence, and treatment resistance. The inability to completely target and remove CSCs is a considerable obstacle in tumor treatment. Therefore, drugs and therapeutic strategies that can effectively intervene with CSCs are essential for the treatment of different tumor types. However, the current strategies and efficacy of targeted elimination of CSCs are very limited. Oxidative stress has been recognized to play a crucial role in cancer pathophysiology. Moreover, reactive oxygen species (ROS) production and imbalance of the built-in cellular antioxidant defense system are hallmarks of tumor and cancer etiology. The current paper will focus on the regulation and mechanism behind oxidative stress in tumors and cancer stem cells and its tumor therapy applications. Additionally, the article discusses the role of CSCs in causing tumor treatment resistance and recurrence based on a redox perspective. The study also emphasizes that targeted modulation of oxidative stress in CSCs has great potential in tumor therapy, providing novel prospects for tumor therapy.

Phytochemicals are richest source of medicines since human history. Cirsium japonicum (Asteraceae), along with other members in the genus are a rich source of flavonoids, polyacetylenes, acetylenes, phenolic acids, phenylpropanoids, sterols, terpenoids and numerous other compounds. Current study aimed to describe an updated review of the literature on the hidden potential of the C. japonicum extracts and its active biological components on neurological disorders. Among various active phytochemicals in C. japonicum includes luteolin, hispidulin, cirsimaritin, acacetin, apigenin, diosmetin, linarin, pectolinarin, and silybin B. Flora of China has been reported around 50 Cirsium species, of which 13 species are reported to be used for treatment of stopping bleedings, removing blood stasis, reducing swelling, treating bleeding syndrome and neurodegenerative disorders like Alzheimer disease (AD). In addition, C. japonicum enhances antioxidant and anticancer activities at cellular level. Moreover, antidepressant potential of ethanol extracts of C. japonicum has also been well described are primarily due to positive modulatory impacts on GABAA receptor (GABAAR) complex. The presence of huge number of active ingredients report in multiple plant species altogether in C. japonicum, appealing for extensive studies for indepth examination of mechanisms and ultimately their usage in clinical trials.

Drug discovery (DD) has an unknown history since the origin of mankind with the process of the trial-and-error method. Modern-day DD primarily straddles three main periods, i.e., the nineteenth century, based on DD by chance by the medicinal chemists; the twentieth century, which spans the exploration and reporting of new drug structures; and finally, the twenty-first century, in which all known structures in conjunction with novel techniques, viz., molecular modeling, combinatorial chemistry, and automated high-throughput screening, led to huge advances in DD. In the start, the scientists examine the natural products themselves to find the exact effects. The isolation of active phytochemicals started in the early nineteenth century, while the advancement in chemical and biological sciences has led the modern DD and development. Moreover, recombinant DNA technology revolutionized the development of potential drugs with higher accuracy and precision. In addition, the onset of the “omics” (proteomics, genomics, metabolomics, etc.) era has boosted the increase in biopharmaceutical drugs approved by the FDA/EMEA for clinical uses. Currently, digital and disruptive technologies such as network pharmacology and molecular docking studies are changing the scenario of DD and development by producing more efficient, personalized drugs with little or no harm at all.

The present study aims to scientifically validate certain pharmacological activities of Euphorbia prostrata ( E. prostrata ) plant extracts and investigate their anti-diabetic, anti-depressant, and anti-anxiety effects. The extraction process employed the Soxhlet apparatus method, using methanol as the solvent. Thirty albino mice were purchased from the local market and divided into five groups, each comprising six mice. Group I served as the negative control, while Group II acted as the positive control. Groups III and IV received two different concentrations (150 and 300 mg/kg) of methanolic plant extract, and Group V was treated with the standard drug Glibenclamide at 10 mg/kg. Blood glucose levels were measured using a glucometer. In diabetic control mice treated with high doses of the plant extract, the blood glucose-lowering impact was more pronounced during this period. Glibenclamide also reduced glucose concentrations comparably to the high dose of plant extract. The anti-diabetic effect of mice administered 300 mg/kg methanol extract paralleled that of mice receiving 10 mg/kg Glibenclamide on the 31st day. To evaluate the anti-depressant activity of E. prostrata , the forced swim test, tail suspension test, and sucrose preference test were conducted. Similarly, the anti-anxiety activity was assessed through the open field test, novel object recognition test, and elevated plus maze test. These tests were carried out on days 1st, 15th, and 30th, and on days 2nd, 16th, and 31st during treatment, respectively, except for the novel object recognition test, which was performed on the last two days of treatment. Results from the behavioural tests indicated that E. prostrata exhibited a potent effect against depressive and anxiolytic behaviour. Statistical analysis using one-way ANOVA presented all results as mean ± SD, with significance considered at P < 0.05.

Objective Polygonum multiflorum Thunb. (PMT) is a widely used traditional Chinese herbal medicine with a variety of pharmacological effects. This study investigates the chemical composition of a water extract of PMT and its potential as a therapy for osteoarthritis (OA). Methods The components of the aqueous extract of PMT were determined using high-performance liquid chromatography (HPLC). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of a gene expression dataset downloaded from the Gene Expression Omnibus (GEO) were performed using Limma in R language. Differential chondrocyte metabolites were determined using gas chromatography-mass spectrometry (GC-MS) before and after treatment. Results The water extract of PMT showed good ability in improving OA, and the content of the active ingredient emodin increased significantly after processing. Analysis of the GEO database further demonstrated a strong association between OA and metabolic pathways. Emodin promotes chondrocyte proliferation and significantly reduces the number of inflammatory factors. The metabolomic results showed that emodin affected five metabolic pathways related mainly to primary bile acid biosynthesis, steroid biosynthesis, and biosynthesis of unsaturated fatty acids. Conclusions This study revealed the pharmacological effects of PMT and emodin as the main active components, thereby providing a scientific basis for the treatment of OA. Graphical abstract http://links.lww.com/AHM/A51

Scientists provide initial biochemical screenings with recombinant pure severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) main protease (Mpro) to discover prospective lead compounds for future coronavirus disease-19 (COVID-19) therapies because viral proteases, after polymerases, are the most likely targets for antiviral drug development. Quinones attach to cysteine-rich proteins, and COVID-19 central protease contains a Cys145-rich active site. The antiviral action of five embelin-containing plant products from Bangladesh against influenza virus A/Puerto Rico/8/34 (H1N1) MDCK infected cells was examined. All the evidence pointed to scaffold simplification and changing the shikonin naphthazarin nucleus as appropriate approaches for reducing shikonin cytotoxicity as a natural SARS-CoV-2 Mpro inhibitor. As a part of an extensive investigation of the biological properties of naphthoquinones with shikonin as a lead, and to contribute to drug discovery against COVID-19, the present study led to the development of juglone and its enhanced version as potent and effective Mpro inhibitors of SARS-CoV-2, which are promising antiviral medication candidates awaiting further analysis. A fluorescently labeled short peptide carrying a Q-S carboxyl link was used to test the inhibitory activity of synthesized quinones on Mpro of SARS-CoV-2. In the first library of chemicals, the capacity of several natural naphthoquinones and synthetic vitamin K3 was determined to inhibit SARS-CoV-2 Mpro at 10 mM. According to a process described in a recent study on the suppression of SARS-CoV-2 Mpro by a methide quinone Celastrol, while attacking the carbonyl carbon, the development of the S–C covalent bond results in a tetrahedral output where the bond develops at the same carbon to which the hydroxy group is connected.

The present study aimed to recognize the recent literature to highlight the pharmacological impacts and highlight the therapeutic potential of the active molecule eriocitrin. Citrus limon are a good resource of the flavanone eriocitrin (eriodictyol 7-O-β-D-rutinoside). Eriocitrin has potent biological actions due to its strong antioxidant, antitumor, anti-allergic, antidiabetic and anti-inflammatory activities. Eriocitrin is more potent in suppressing oxidative stress in diabetes mellitus (DM) and other chronic diseases incurred by excessive oxidative stress. During metabolism, eriocitrin is metabolized by gut microbiota, and a chain of molecules such as eriodictyol, methy-eriodictyol, 3,4-dihydroxyhydrocinnamic acid (DHCA), and much more conjugated molecules. More in-depth studies are recommended to explore this drug for clinical trials.