Withanone as an Emerging Anticancer Agent and Understanding Its Molecular Mechanisms: Experimental and Computational Evidence.

Despite decades of research and effort, treating cancer is still a challenging task. Current conventional treatments are still unsatisfactory to fully eliminate and prevent re-emergence or relapses, and targeted or personalised therapy, which are more effective in managing cancer, may be unattainable or inaccessible for some. In the past, research in natural products have yielded some of the most commonly used cancer treatment drugs known today. Hence it is possible more are awaiting to be discovered. Withanone, a common withanolide found in the Ayurvedic herb Withania somnifera, has been claimed to possess multiple benefits capable of treating cancer. This review focuses on the potential of withanone as a safe cancer treatment drug based on the pharmacokinetic profile and molecular mechanisms of actions of withanone. Through these in silico and in vitro studies discussed in this review, withanone showspotent anticancer activities and interactions with molecular targets involved in cancer progression. Furthermore, some evidences also show the selective killing property of withanone, which highlights the safety and specificity of withanone in targeting cancer cell. By compiling these evidences, this review hopes to spark interest for future research to be conducted in more extensive studies involving withanone to generate more data, especially involving in vivo experiments and toxicity evaluation of withanone.

Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms.

Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay.

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.

An Evaluation of Antimicrobial, Anticancer, Anti-Inflammatory and Antioxidant Activities of Silver Nanoparticles Synthesized from Leaf Extract of Madhuca longifolia Utilizing Quantitative and Qualitative Methods.

In the current decade, nanoparticles are synthesized using solvents that are environmentally friendly. A number of nanoparticles have been synthesized at room temperature using water as a solvent, such as gold (Au) and silver (Ag) nanoparticles. As part of nanotechnology, nanoparticles are synthesized through biological processes. Biological methods are the preferred method for the synthesis of inorganic nanoparticles (AgNPs) as a result of their simple and non-hazardous nature. Nanoparticles of silver are used in a variety of applications, including catalysts, spectrally selective coatings for solar absorption, optical objectives, pharmaceutical constituents, and chemical and biological sensing. Antimicrobial agents are among the top uses of silver nanoparticles. In the current study, silver nanoparticles were biologically manufactured through Madhuca longifolia, and their antibacterial activity against pathogenic microorganisms, anticancer, anti-inflammatory, and antioxidant activities were assessed. UV-Vis spectroscopy, XRD (X-ray diffraction), transmission electron microscopy, Zeta Potential, and FTIR were used to characterize silver nanoparticles. The current work describes a cheap and environmentally friendly method to synthesize silver nanoparticles from silver nitrate solution by using plant crude extract as a reducing agent.

Impact of Prolonged COVID-19 Lockdown on Body Mass Index, Eating Habits, and Physical Activity of University Students in Bangladesh: A Web-Based Cross-Sectional Study.

Objectives: This current study aims to assess the prevalence and factors associated with body mass index (BMI), dietary patterns, and the extent of physical activities among university students following the prolonged coronavirus disease 2019 (COVID-19) lockdown in Bangladesh. Methods: A cross-sectional web-based survey was conducted between July 10 to August 10, 2021, through a pre-designed Google Form to collect the data from Bangladeshi university students (age: ≥18 years). Informed consent was electronically obtained from each participant, and a simple snowball technique was employed during the sampling. Frequency and percentage distribution, paired t-test, chi-square [χ2] test, and multinomial and binary logistic regression analyses were consecutively applied to analyze the collected data. Results: Among the total participants (n = 1,602), 45.1% were female and 55.6% were 22-25 years' age group students. The BMI (mean ± standard deviation, SD) during the COVID-19 lockdown was 23.52 ± 7.68 kg/m2, which was 22.77 ± 4.11 kg/m2 during the pre-lockdown period (mean difference = 0.753; p < 0.001). The multinomial logistic regression analysis found a significant impact of gender [male vs. female: adjusted relative risk ratio (RRR) = 1.448; 95% confidence interval (CI) = 1.022, 2.053; p = 0.037], age (years) (<22 vs. >25: RRR =0.389, 95% CI = 0.213,0.710; p = 0.002, and 22-25 vs. >25: RRR = 0.473, 95% CI = 0.290, 0.772; p = 0.003), monthly family income (BDT) (<25,000 vs. >50,000: RRR = 0.525, 95% CI = 0.334,0.826; p = 0.005), university type (public vs. private: RRR = 0.540, 95% CI = 0.369, 0.791; p = 0.002), eating larger meals/snacks (increased vs. unchanged: RRR = 2.401, 95% CI = 1.597, 3.610; p < 0.001 and decreased vs. unchanged: RRR = 1.893, 95% CI = 1.218, 2.942; p = 0.005), and verbally or physically abuse (yes vs. no: RRR = 1.438, 95% CI = 0.977, 2.116; p = 0.066) on obesity during COVID-19 pandemic. Besides, the female students and those who have constant eating habits, were more likely to be underweight. Additionally, the binary logistic regression analysis found that the students from private universities [others vs. private: adjusted odds ratio (AOR) = 0.461, 95% CI = 0.313, 0.680; p < 0.001], urban areas (urban vs. rural: AOR = 1.451, 95% CI = 1.165, 1.806; p = 0.001), wealthier families (<25,000 BDT vs. >50,000 BDT: AOR = 0.727, 95% CI = 0.540, 0.979; p = 0.036), and who were taking larger meals/snacks (increased vs. unchanged: AOR = 2.806, 95% CI = 2.190, 3.596; p < 0.001) and had conflicts/arguments with others (no vs. yes: AOR = 0.524, 95% CI = 0.418, 0.657; p < 0.001), were significantly more physically inactive. Finally, the level of education and smoking habits significantly influenced the eating habits of university students during the extended strict lockdown in Bangladesh. Conclusion: The current findings would be helpful tools and evidence for local and international public health experts and policymakers to reverse these worsening effects on students mediated by the prolonged lockdown. Several effective plans, programs, and combined attempts must be earnestly implemented to promote a smooth academic and daily life.

Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors.

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a-5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.

The Design, Synthesis, and Evaluation of Diaminopimelic Acid Derivatives as Potential dapF Inhibitors Preventing Lysine Biosynthesis for Antibacterial Activity.

We created thiazole and oxazole analogues of diaminopimelic acid (DAP) by replacing its carboxyl groups and substituting sulphur for the central carbon atom. Toxicity, ADME, molecular docking, and in vitro antimicrobial studies of the synthesized compounds were carried out. These compounds displayed significant antibacterial efficacy, with MICs of 70-80 µg/mL against all tested bacteria. Comparative values of the MIC, MBC, and ZOI of the synthesized compound were noticed when compared with ciprofloxacin. At 200 µg/mL, thio-DAP (1) had a ZOI of 22.67 ± 0.58, while ciprofloxacin had a ZOI of 23.67 ± 0.58. To synthesize thio-DAP (1) and oxa-DAP (2), l-cysteine was used as a precursor for the L-stereocenter (l-cysteine), which is recognized by the dapF enzyme's active site and selectively binds to the ligand's L-stereocenter. Docking studies of these compounds were carried out using the programme version 11.5 Schrodinger to reveal the hydrophobic and hydrophilic properties of these complexes. The docking scores of compounds one and two were -9.823 and -10.098 kcal/mol, respectively, as compared with LL-DAP (-9.426 kcal/mol.). This suggests that compounds one and two interact more precisely with dapF than LL-DAP. Chemicals one and two were synthesized via the SBDD (structure-based drug design) approach and these act as inhibitors of the dapF in the lysine pathway of bacterial cell wall synthesis.

Nutraceutical potentials of algal ulvan for healthy aging.

Several theories for aging are constantly put forth to explain the underlying mechanisms. Oxidative stress, DNA dysfunction, inflammation, and mitochondrial dysfunction, along with the release of cytochrome c are some of these theories. Diseases such as type 2 diabetes mellitus, intestinal dysfunction, cardiovascular diseases, hepatic injury, and even cancer develop with age and eventually cause death. Ulva polysaccharides, owing to their special structures and various functions, have emerged as desirable materials for keeping healthy. These polysaccharide structures are found to be closely related to the extraction methods, seaweed strains, and culture conditions. Ulvan is a promising bioactive substance, a potential functional food, which can regulate immune cells to augment inflammation, control the activity of aging-related genes, promote tumor senescence, enhance mitochondrial function, maintain liver balance, and protect the gut microbiome from inflammatory attacks. Given the desirable physiochemical and gelling properties of ulvan, it would serve to improve the quality and shelf-life of food.

The anti-hyperuricemic effects of green alga Enteromorpha prolifera polysaccharide via regulation of the uric acid transporters in vivo.

A novel polysaccharide obtained from Enteromorpha prolifera (EPP) was purified through diethylaminoethyl cellulose-52 and Sephadex G-75 chromatography. Fourier transform infrared spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance (NMR) spectroscopy were employed to analyse the structure of EPP. It mainly comprised rhamnose, glucuronic acid, galactose, arabinose, and xylose at a molar ratio of 20.45:12.74:10.99:5.84:1.95, and its average molecular weight was 46.56 kDa. The seven major glycosidic residues identified by NMR were as follows: →2)-α-L-Araf-(1→, →2)-α-L-Rhap-(1→, →4)-α-L-Rhap-(1→, →2,6)-ß-D-Galp-(1→, →4)-ß-D-GlcpA-(1→, →3,4)-ß-D-GlcpA-(1→, and →4)-ß-Xylp-(1→. The effect of EPP on hyperuricemic mice was determined by analysing correlative general physical parameters, renal histopathology, renal gene expressions, and gut microbiome. EPP significantly reduced serum uric acid (UA), serum blood urea nitrogen, serum xanthine oxidase (XOD), and hepatic XOD as well as improved histological parameters in hyperuricemic mice. Furthermore, mRNA and protein expression analyses showed the upregulation of UA excretion genes such as ABCG2, OAT1, and NPT1 and downregulation of UA resorption gene URAT1. Moreover, EPP maintained the stability of the intestinal flora and confirmed that Parasutterella is closely related to the regulation of hyperuricemia. This study is the first to demonstrate the anti-hyperuricemic activity of EPP and highlight its therapeutic potential for hyperuricemia-related diseases.

Phytochemical and Therapeutic Potential of Citrus grandis (L.) Osbeck: A Review.

Citrus grandis or Citrus maxima, widely recognized as Pomelo is widely cultivated in many countries because of their large amounts of functional, nutraceutical and biological activities. In traditional medicine, various parts of this plant including leaf, pulp and peel are used for generations as they are scientifically proven to have therapeutic potentials and safe for human use. The main objective of this study was to review the different therapeutic applications of Citrus grandis and the phytochemicals associated with its medicinal values. In this article different pharmacological properties like antimicrobial, antitumor, antioxidant, anti-inflammatory, anticancer, antiepileptic, stomach tonic, cardiac stimulant, cytotoxic, hepatoprotective, nephroprotective, and anti-diabetic activities of the plant are highlighted. The enrichment of the fruit with flavonoids, polyphenols, coumarins, limonoids, acridone alkaloids, essential oils and vitamins mainly helps in exhibiting the pharmacological activities within the body. The vitamins enriched fruit is rich in nutritional value and also has minerals like calcium, phosphorous, sodium and potassium, which helps in maintaining the proper health and growth of the bones as well as the electrolyte balance of the body. To conclude, various potential therapeutic effects of Citrus grandis have been demonstrated in recent literature. Further studies on various parts of fruit, including pulp, peel, leaf, seed and it essential oil could unveil additional pharmacological activities which can be beneficial to the mankind.

Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

Coriandrum sativum L.: A Review on Ethnopharmacology, Phytochemistry, and Cardiovascular Benefits.

Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The cardiovascular benefits of C. sativum have not been summarized before, hence this review aims to further evaluate and discuss its effectiveness in cardiovascular diseases, according to the recent literature. An electronic search for literature was carried out using the following databases: PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews. Articles were gathered from the inception of the database until August 2021. Moreover, the traditional uses and phytochemistry of coriander were surveyed in the original resources and summarized. As a result, most of the studies that cover cardiovascular benefits and fulfilled the eligibility criteria were in vivo, while only a few were in vitro and clinical studies. In conclusion, C. sativum can be deemed a functional food due to its wide range of cardiovascular benefits such as antihypertensive, anti-atherogenic, antiarrhythmic, hypolipidemic as well as cardioprotective effects.

Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects.

Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications such as, insulin, sulfonylureas, dipeptyl peptidase (DPP) 4 inhibitors and glucose-dependent insulinotropic peptide (GLP-1) analogues increased the additional risk of different cancers to diabetic patients. Conversely, metformin has drawn attention among physicians and researchers since its use as antidiabetic drug exhibited beneficial effect in the prevention and treatment of cancer in diabetic patients as well as an independent anticancer drug. This review aims to provide the comprehensive information on the use of metformin at preclinical and clinical stages among colorectal cancer patients. We highlight the efficacy of metformin as an anti-proliferative, chemopreventive, apoptosis inducing agent, adjuvant, and radio-chemosensitizer in various colorectal cancer models. This multifarious effects of metformin is largely attributed to its capability in modulating upstream and downstream molecular targets involved in apoptosis, autophagy, cell cycle, oxidative stress, inflammation, metabolic homeostasis, and epigenetic regulation. Moreover, the review highlights metformin intake and colorectal cancer risk based on different clinical and epidemiologic results from different gender and specific population background among diabetic and non-diabetic patients. The improved understanding of metformin as a potential chemotherapeutic drug or as neo-adjuvant will provide better information for it to be used globally as an affordable, well-tolerated, and effective anticancer agent for colorectal cancer.

Comprehensive Review on Phytochemicals, Pharmacological and Clinical Potentials of Gymnema sylvestre.

Gymnema sylvestre is a plant included in Apocynaceae family and is located in many regions of Asia, Africa and Australia. This plant is widely used as a traditional therapy for different purposes. Even now it is being used as a dietary supplement due to its numerous therapeutic uses. It is known to have blood glucose lowering potential and, thus, is widely used in traditional and Ayurvedic systems of medicine. It renders glucose lowering activity due to the presence of phytochemicals, such as gurmarin, gymnemic acid as well as gymnemasaponins. Gymnema sylvestre is also known to have anti-oxidant, antibiotic, anti-inflammatory, antiviral, gastro and hepatoprotective, anticancer and lipid-lowering activities. This review discusses in details on different pharmacological and clinical potentials of Gymnema sylvestre and its chemical constituents associated with its therapeutic potentials.

Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways.

A novel heteropolysaccharide from Grifola frondosa named GFP-W has been isolated and purified by DEAE Sephadex A-52 chromatography. Gas chromatography, fourier transform infrared spectroscopy, one-dimensional (1H- and 13C-) and two-dimensional (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) nuclear magnetic resonance spectroscopy were used to characterize its structure. The average molecular weight of GFP-W was 66.1 kDa. GFP-W mainly contained four kinds of linkage type units as ß-D-GlcpA→, 1,2,6-α-Gal, →2)-α-Manp→, and →3)-α-L-Fucp-(1→. It could significantly increase the uptake of glucose in dexamethasone induced insulin resistant HepG2 cells by improving the mRNA and protein expression of insulin receptor substrate 1, phosphatidylinositol-3-kinase, and glucose transporter 4 upregulation and c-Jun N-terminal Kinase 1 downregulation. Moreover, antidiabetic activities of GFP-W were associated with significant changes in the extent of protein lysine acetylation, crotonylation, and succinylation levels. Our results provide a new hypoglycemic therapeutic role and an in-depth analysis on molecular mechanisms upon polysaccharides from G. frondosa.

Antiproliferative and apoptosis inducing effects of citral via p53 and ROS-induced mitochondrial-mediated apoptosis in human colorectal HCT116 and HT29 cell lines.

Despite various anticancer reports, antiproliferative and apoptosis inducing activity of citral in HCT116 and HT29 cells have never been reported. This study aimed to evaluate the cytotoxic and apoptosis inducing effects of citral in colorectal cancer cell lines. The citral-treated cells were subjected to MTT assay followed by flow cytometric Annexin V-FITC/PI, mitochondrial membrane potential and intracellular reactive oxygen species (ROS) determination. The apoptotic proteins expression was investigated by Western blot analysis. Citral inhibited the growth of HCT116 and HT29 cells by dose- and time-dependent manner without inducing cytotoxicity in CCD841-CoN normal colon cells. Flow cytometric analysis showed that citral (50-200µM; 24-48h) induced the externalization of phoshpotidylserine and reduced the mitochondrial membrane potential in HCT116 and HT29 cells. Citral elevated intracellular ROS level while attenuating GSH levels in HCT116 and HT29 cells which were reversed with N-acetycysteine (2mM) pre-treatment indicating that citral induced mitochondrial-mediated apoptosis via augmentation of intracellular ROS. Citral induced the phosphorylation of p53 protein and the expression of Bax while decreasing Bc-2 and Bcl-xL expression which promoted the cleavage of caspase-3. Collectively, our data suggest that citral induced p53 and ROS-mediated mitochondrial-mediated apoptosis in human colorectal cancer HCT116 and HT29 cells.

Prophetic medicine as potential functional food elements in the intervention of cancer: A review.

Amounting scientific evidences have revealed the antitumor, antimetastatic, antiangiogenic, antiproliferative, chemopreventive and neo-adjuvant efficacy of Prophetic Medicine in various in vitro, in vivo and clinical cancer models. Prophetic Medicine includes plants, dietary materials or spices that were used as remedy recipes and nutrition by the great Prophet Mohammed (peace be upon him) to treat various ailments. Prophetic medicine is the total authentic Hadith narrated by the Prophet (PBUH) in relation to medicine, whether Qur'anic verses or honourable Prophetic Hadith. The ability of functional foods from Prophetic Medicine to modulate various signalling pathways and multidrug resistance conferring proteins with low side-effects exemplify their great potential as neo-adjuvants and/or chemotherapeutics. The present review aims to provide the collective in vitro, in vivo, clinical and epidemiology information of Prophetic Medicines, and their bioactive constituents and molecular mechanisms as potential functional foods for the management of cancer.

Enhancement of the production of L-glutaminase, an anticancer enzyme, from Aeromonas veronii by adaptive and induced mutation techniques.

Microbial anti-cancer enzymes have been proven to be effective and economical agents for cancer treatment. Aeromonas veronii has been identified as a microorganism with the potential to produce L-glutaminase, an anticancer agent effective against acute lymphocytic leukaemia. In this study, a selective medium of Aeromonas veronii was used to culture the microorganism. Strain improvement was done by adaptive and induced mutational techniques. A selective minimal agar media was incorporated for the growth of the strain which further supports adaptive mutation. Strains were also UV-irradiated and successively treated with N-methyl-N'-nitro-N-nitrosoguanidine to find a resilient strain capable of producing L-glutaminase efficiently. The Plackett-Burman design and central composite designs were used to screen and optimize additional carbon and nitrogen sources. Adaptive mutation resulted in promising yield improvements compared to native strain (P<0.001). The mean yield of 30 treated colonies from the induced mutation was significantly increased compared to the non-induced strain (P< 0.001). The economically feasible statistical designs were found to reinforce each other in order to maximize the yield of the enzyme. The interactions of nutrient factors were understood from the 3D response surface plots. The model was found to be a perfect fit in terms of maximizing enzyme yield, with the productivity improving at every stage to a fourfold output of enzyme (591.11 ±7.97 IU/mL) compared to the native strain (135±3.51 IU/mL).

Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic applications of Clinacanthus nutans (Burm. f.) Lindau: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinacanthus nutans (Burm. f.) Lindau, a widely used medicinal plant, is extensively grown in tropical Asia and Southeast Asian countries. C. nutans, with its broad spectrum of pharmacological activities, has been traditionally used to treat cancer, inflammatory disorders, diabetes, insect bites, and skin problems, consumed as a vegetable, mixed with fresh juices, in concoctions, and as a whole plant. The present review analyzes the advances in the ethnopharmacology, phytochemistry, pharmacology, and toxicology of C. nutans. In addition, the needs and perspectives for future investigation of this plant are addressed. AIM OF THE REVIEW: This review aims to provide a comprehensive report on the ethnomedicinal use, phytochemistry, pharmacological activities, molecular mechanisms, and nutritional values of C. nutans. The present review will open new avenues for further in-depth pharmacological studies of C. nutans for it to be developed as a potential nutraceutical and to improve the available products in the market. MATERIAL AND METHODS: All the available information on C. nutans was collected using the key words "Clinacanthus nutans" and/or "ethnomedicine" and/or "phytochemicals" and/or "anticancer" and/or "anti-inflammatory" and/or "antiviral" through an electronic search of the following databases: PubMed, Web of Science, EMBASE, Cochrane Library, Clinical Trials.org, SciFinder Scholar, Scopus, and Google Scholar. In addition, unpublished materials, Ph.D. and M.Sc. dissertations, conference papers, and ethnobotanical textbooks were used. The Plant List (www.theplantlist.org) and International Plant Name Index databases were used to validate the scientific name of the plant. RESULTS: The literature supported the ethnomedicinal uses of C. nutans as recorded in Thailand, Indonesia, and Malaysia for various purposes. Bioactivities experimentally proven for C. nutans include cytotoxic, anticancer, antiviral, anti-inflammatory, immunomodulatory, antidiabetic, antioxidant, antihyperlipidemic, antimicrobial, and chemotherapeutic (in aquaculture) activities. Most of these activities have so far only been investigated in chemical, cell-based, and animal assays. Various groups of phytochemicals including five sulfur-containing glycosides, eight chlorophyll derivatives, nine cerebrosides, and a monoacylmonogalactosyl glycerol are present in C. nutans. The presence of two glycerolipids, four sulfur-containing compounds, six known flavones, a flavanol, four flavonols, two phytosterols, one polypeptide, and various phenolics and fatty acids largely influences its diverse bioactivities. Numerous reports justify the ethnomedicinal use of C. nutans as an antiviral agent in treating herpes simplex virus and varicella-zoster virus infections and as part of a traditional anticancer anti-inflammatory concoction agent for various inflammatory diseases. C. nutans tea was reported to have a good percentage of carbohydrate, crude protein, minerals, essential amino acids, nonessential amino acids, and essential fatty acids. Acute, subacute, and subchronic toxicity studies demonstrated that oral administration of ethanol and methanol extracts of C. nutans to male Swiss albino mice and male Sprague-Dawley (SD) rats, respectively, did not lead to any toxicity or adverse effects on the animal behavior and organs when used in amounts as high as 2g/kg. CONCLUSION: The collected literatures demonstrated that, as an important traditional medicine, C. nutans is a promising ethnomedicinal plant with various extracts and bioactive compounds exhibiting multifarious bioactivities. However, it is important for future studies to conduct further in vitro and in vivo bioactivity evaluations systematically, following the standard pharmacology guidelines. It is crucial to elucidate in-depth molecular mechanisms, structure-activity relationships, and potential synergistic and antagonistic effects of multi-component extracts and bioactive constituents derived from C. nutans. Further studies should also focus on comprehensive toxicity that includes long-term effects and adverse effects on target organs of C. nutans and bioactive compounds in correlation with the specific pharmacological effects.

The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles. Several functional foods have therapeutic potential to treat chronic diseases including diabetes. The therapeutic potential of pomegranate has been stated by multitudinous scientists. The present study aimed to evaluate the effects of pomegranate juice and seed powder on the levels of plasma glucose and insulin, inflammatory biomarkers, lipid profiles, and health of the pancreatic islets of Langerhans in streptozotocin (STZ)-nicotinamide (NAD) induced T2DM Sprague Dawley (SD) rats. METHODS: Forty healthy male SD rats were induced to diabetes with a single dose intra-peritoneal administration of STZ (60 mg/kg b.w.) - NAD (120 mg/kg b.w.). Diabetic rats were orally administered with 1 mL of pomegranate fresh juice (PJ) or 100 mg pomegranate seed powder in 1 mL distilled water (PS), or 5 mg/kg b.w. of glibenclamide every day for 21 days. Rats in all groups were sacrificed on day 22. The obtained data was analyzed by SPSS software (v: 22) using One-way analysis of variance (ANOVA). RESULTS: The results showed that PJ and PS treatment had slight but non-significant reduction of plasma glucose concentration, and no impact on plasma insulin compared to diabetic control (DC) group. PJ lowered the plasma total cholesterol (TC) and triglyceride (TG) significantly, and low-density lipoproteins (LDL) non-significantly compared to DC group. In contrast, PS treatment significantly raised plasma TC, LDL, and high-density lipoproteins (HDL) levels compared to the DC rats. Moreover, the administration of PJ and PS significantly reduced the levels of plasma inflammatory biomarkers, which were actively raised in diabetic rats. Only PJ treated group showed significant repairment and restoration signs in islets of Langerhans. Besides, PJ possessed preventative impact against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals almost 2.5 folds more than PS. CONCLUSIONS: Our findings suggest that active constituents with high antioxidant properties present in PJ are responsible for its anti-hyperlipidemic and anti-inflammatory effects, likewise the restoration effect on the damaged islets of Langerhans in experimental rats. Hence, the pharmacological, biochemical, and histopathological profiles of PJ treated rats obviously indicated its helpful effects in amelioration of diabetes-associated complications.