Phenanthroindolizidine Alkaloids Secondary Metabolites Diversity in Medicinally Viable Plants of the Genus Tylophora.

Plants of the genus Tylophora have commonly been used in traditional medicine in various communities, especially in the tropical and subtropical regions of climatic zones. Of the nearly 300 species reported in the Tylophora genus, eight are primarily used in various forms to treat a variety of bodily disorders based on the symptoms. Certain plants from the genus have found use as anti-inflammatory, anti-tumor, anti-allergic, anti-microbial, hypoglycemic, hypolipidemic, anti-oxidant, smooth muscle relaxant, immunomodulatory, and anti-plasmodium agents, as well as free-radical scavengers. Pharmacologically, a few plant species from the genus have exhibited broad-spectrum anti-microbial and anti-cancer activity, which has been proven through experimental evaluations. Some of the plants in the genus have also helped in alcohol-induced anxiety amelioration and myocardial damage repair. The plants belonging to the genus have also shown diuretic, anti-asthmatic, and hepato-protective activities. Tylophora plants have afforded diverse structural bases for secondary metabolites, mainly belonging to phenanthroindolizidine alkaloids, which have been found to treat several diseases with promising pharmacological activity levels. This review encompasses information on various Tylophora species, their distribution, corresponding plant synonyms, and chemical diversity of the secondary metabolic phytochemicals as reported in the literature, together with their prominent biological activities.

The nutraceutical properties and health benefits of pseudocereals: a comprehensive treatise.

This review article depicts the possible replacement of staple cereal sources with some pseudocereals like Chia, Quinoa, Buckwheat, and Amaranth, which not only provide recommended daily allowance of all nutrients but also help to reduce the chances of many non-communicable infections owing to the presence of several bioactive compounds. These pseudocereals are neglected plant seeds and should be added in our routine diet. Besides, they can serve as nutraceuticals in combating various diseases by improving the health status of the consumers. The bioactive compounds like rutin, quercetin, peptide chains, angiotensin I, and many other antioxidants present in these plant seeds help to reduce the oxidative stress in the body which leads toward better health of the consumers. All these pseudocereals have high quantity of soluble fiber which helps to regulate bowel movement, control hypercholesterolemia (presence of high plasma cholesterol levels), hypertension (high blood pressure), and cardiovascular diseases. The ultimate result of consumption of pseudocereals either as a whole or in combination with true cereals as staple food may help to retain the integrity of the human body which increases the life expectancy by slowing down the aging process.

Therapeutic application of carvacrol: A comprehensive review.

Carvacrol is a major natural constituent and is significantly present as an essential oil in aromatic plants and is well known for its numerous biological activities. Therapeutic properties of carvacrol have been demonstrated as anti-oxidant, anticancer, diabetes prevention, cardioprotective, anti-obesity, hepatoprotective and reproductive role, antiaging, antimicrobial, and immunomodulatory properties. The carvacrol biosynthesis has been mediated through mevalonate pathway. Carvacrol has the anticancer ability against malignant cells via decreasing the expressions of matrix metalloprotease 2 and 9, inducing apoptosis, enhancing the expression of pro-apoptotic proteins, disrupting mitochondrial membrane, suppressing extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signal transduction, and also decreasing the phosphoinositide 3-kinase/protein kinase B. It also decreased the concentrations of alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase, and gamma-glutamyl transpeptidase as well as also restored liver function, insulin level, and plasma glucose level. Carvacrol also has been found to exert antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Coagulase-negative staphylococcus, Salmonella spp., Enterococcus sp. Shigella, and Escherichia coli. The current review article summarizes the health-promoting perspectives of carvacrol through various pathways.

Bilosomes as a promising nanoplatform for oral delivery of an alkaloid nutraceutical: improved pharmacokinetic profile and snowballed hypoglycemic effect in diabetic rats.

Diabetes mellitus is a life-threatening metabolic disease. At the moment, there is no effective treatment available to combat it. In this study, we aimed to develop berberine-loaded bilosomes (BER-BLS) to boost the oral bioavailability and therapeutic efficacy of berberine, a natural antidiabetic medication. The BER-BLS was fabricated using a thin-film hydration strategy and optimized using a central composite design (face-centered). The average vesicle size, entrapment efficiency, and surface charge of the optimized BER-BLS preparation were 196.5 nm, 89.7%, (-) 36.4 mV, respectively. In addition, it exhibited higher stability and better-sustained release of berberine than the berberine solution (BER-SOL). BER-BLS and BER-SOL were administered to streptozocin-induced diabetic rats. The optimized BER-BLS formulation had a significant hypoglycemic impact, with a maximum blood glucose decrease of 41%, whereas BER-SOL only reduced blood glucose by 19%. Furthermore, the pharmacological effect of oral BER-BLS and BER-SOL corresponded to 99.3% and 31.7%, respectively, when compared to subcutaneous insulin (1 IU). A pharmacokinetic analysis found a 6.4-fold rise in the relative bioavailability of berberine in BER-BLS when compared to BER-SOL at a dosage of 100 mg/kg body weight. Histopathological investigation revealed that BER-BLS is suitable for oral administration. Our data demonstrate that BLS is a potential nanocarrier for berberine administration, enhancing its oral bioavailability and antidiabetic activity.

Evaluation of the active constituents of Nilavembu Kudineer for viral replication inhibition against SARS-CoV-2: An approach to targeting RNA-dependent RNA polymerase (RdRp).

The World Health Organization has declared the novel coronavirus (COVID-19) outbreak a global pandemic and emerging threat to people in the 21st century. SARS-CoV-2 constitutes RNA-Dependent RNA Polymerase (RdRp) viral proteins, a critical target in the viral replication process. No FDA-approved drug is currently available, and there is a high demand for therapeutic strategies against COVID-19. In search of the anti-COVID-19 compound from traditional medicine, we evaluated the active moieties from Nilavembu Kudineer (NK), a poly-herbal Siddha formulation recommended by AYUSH against COVID-19. We conducted a preliminary docking analysis of 355 phytochemicals (retrieved from PubChem and IMPPAT databases) present in NK against RdRp viral protein (PDB ID: 7B3B) using COVID-19 Docking Server and further with AutoDockTool-1.5.6. MD simulation studies confirmed that Orientin (L1), Vitexin (L2), and Kasuagamycin (L3) revealed better binding activity against RdRp (PDB ID: 7B3B) in comparison with Remdesivir. The study suggests a potential scaffold for developing drug candidates against COVID-19. PRACTICAL APPLICATIONS: Nilavembu Kudineer is a poly-herbal Siddha formulation effective against various diseases like cough, fever, breathing problems, etc. This study shows that different phytoconstituents identified from Nilavembu Kudineer were subjected to in silico and ADME analyses. Out of the former 355 phytochemical molecules, Orientin (L1), Vitexin (L2), and Kasuagamycin (L3) showed better binding activity against RdRp viral protein (PDB ID: 7B3B) in comparison with the synthetic repurposed drug. Our work explores the search for an anti-COVID-19 compound from traditional medicine like Nilavembu Kudineer, which can be a potential scaffold for developing drug candidates against COVID-19.

LC/MS Profiling and Gold Nanoparticle Formulation of Major Metabolites from Origanum majorana as Antibacterial and Antioxidant Potentialities.

Origanum majoranum L. is a Lamiaceae medicinal plant with culinary and ethnomedical applications. Its biological and phytochemical profiles have been extensively researched. Accordingly, this study aimed to investigate the chemical composition and the antibacterial and antioxidant properties of O. majoranum high features, as well as to search for techniques for activity optimization. A metabolomics study of the crude extract of O. majoranum using liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC ± HR ± ESI ± MS) was conducted. Five fractions (petroleum ether, dichloromethane, ethyl acetate, n-butanol, and aqueous) were derived from the total extract of the aerial parts. Different chromatographic methods and NMR analysis were utilized to purify and identify the isolated phenolics (high features). Moreover, the antimicrobial, antibiofilm, and antioxidant activity of phenolics were performed. Results showed that metabolomic profiling of the crude extract of O. majoranum aerial parts revealed the presence of a variety of phytochemicals, predominantly phenolics, resulting in the isolation and identification of seven high-feature compounds comprising two phenolic acids, rosmarinic and caffeic acids, one phenolic diterpene, 7-methoxyepirosmanol, in addition to four flavonoids, quercetin, hesperitin, hesperidin, and luteolin. On the other hand, 7-methoxyepirosmanol (OM1) displayed the most antimicrobial and antioxidant potential. Such a phenolic principal activity improvement seems to be established after loading on gold nanoparticles.

Efficiency of Multiple Extraction Solvents on Antioxidant, Cytotoxic, and Phytotoxic Potential of Taraxacum officinale (L.) Weber ex F.H. Wigg. from Poonch Valley, Azad Kashmir, Pakistan.

Background: Different parts of Taraxacum officinale (L.) were used in traditional medicine in various parts of the world for the treatment of health problems, and they possess significant biological activities. The present study aimed to estimate phytochemical and biological activities of T. officinale using different extraction solvents. Methods: Methanolic, acetone, and n-hexane extracts of selected species were prepared, and ten secondary metabolites were examined using standard protocols. The antioxidant activity was performed using three in vitro methods, namely, DPPH assay, total reducing power (TRP) assay, and total antioxidant capacity (TAC). Toxicological analysis was done using the brine shrimp cytotoxic assay and radish seed phytotoxic assay. Results: The T. officinale methanolic extract showed the highest phenolic (178.27 ± 17.17 mg/GAE/g) and flavonoid (18.50 ± 1.64 mg QE/g) contents. Similarly, the methanolic extract also revealed the highest DPPH activity (32.80 ± 9.66 IC50), reducing potential (0.53 ± 0.02 mg/g), and TAC (19.42 ± 0.97 mg/g) as compared to the acetone and n-hexane extracts. The Pearson correlation analysis confirmed a strong positive correlation (r > 0.9) between total phenolic content (TPC), total flavonoid content (TFC), and all antioxidant assays. Furthermore, a heat map displayed the methanolic extract (red color) as a valuable source of phytochemicals and antioxidant agents. Moreover, the T. officinale methanolic extract also showed the highest (7.12 ppm) cytotoxic potential whereas both methanolic and acetone extracts were revealed as moderate phytotoxic agents when compared with the standard. Conclusion: The T. officinale methanolic extract exhibited comparatively notable phytochemicals that are actively involved in antioxidant activities and possess toxicological properties. This upholds the folkloric use of T. officinale as a possible source to develop natural plant-based drugs. Further investigations to isolate bioactive compounds and elements and on their safety need to be conducted.

Effect of Hydroaloholic Extract of Rotula Aquatica Lour on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats: An In Vitro and In Vivo Approach.

One-third of the world population suffer from kidney complications such as acute and chronic renal failure, renal calculi, kidney stones, Fanconi's syndrome and urethritis which doesn't have a proper effective treatment regimen. The current study explores the nephroprotective effect of herbal drug Rotula Aquatica by both In Vitro and In Vivo methods. MTT assay was applied In Vitro to evaluate the nephroprotective effect of R. aquatica leaves extract on HEK 293 cell line. The acute toxicity of the extract was evaluated as per the limit test under the protocol of OECD 423 at a concentration of 2000 mg/kg using 6 female rats. Further, an In Vivo study using the Gentamicin-instigated nephrotoxicity model was carried out for a period of 8 days. Biochemical markers of renal damage, endogenous antioxidants and histopathology were determined to assess the effect of treatment. The In Vitro study using HEK 293 cell line resulted in an EC50 value of 51.50 µg/ml for the extract in comparison to the standard drug Cytsone (12.26 µg/ml). Based on the limit test of OECD 423, doses of 200 and 400 mg/kg were chosen for the study. The results revealed a strong nephroprotective activity at 400 mg/kg in Gentamicin-induced nephrotoxicity against standard drug cystone by restoring the decrement in body weight, renal enzymatic and non-enzymatic antioxidants, creatinine and urea levels in urine and plasma. This indicated that hydroalcoholic extract of Rotula aquatica (HAERA) can prevent the Gentamicin toxicity due to the high content of antioxidant and anti-inflammatory secondary metabolites.

Investigation of Chemical Compositions and Biological Activities of Mentha suaveolens L. from Saudi Arabia.

Mentha is an aromatic plant used since antiquity for its pharmaceutical virtues. The climate of Saudi Arabia favors the growth of aromatic plants including Mentha suaveolens L. The aim of this study is to analyze the volatile oils of different parts of fresh and dried Mentha suaveolens L. grown in Saudi Arabia (Aljouf area) using Gas Chromatography/Mass Spectrometry (GC/MS) and Gas Chromatography Flame Ionization Detector (GC/FID) techniques, to recognize the effect of drying on chemical composition, then to evaluate the antioxidant and antifungal activities of different extracts. In total, 118 compounds were identified via GC/MS and GC/FID, in which carvone is the main volatile constituent (stems, leaves, whole plant 45-64%). This investigation deduces that Mentha belonged to the carvone chemotype. Then, the analysis of non-volatile constituents of fresh and dried Mentha was performed by HPLC. The main phenolic compound of fresh and dried Mentha for different parts was rosmarinic acid (ranging from 28,002.5 to 6558 µg/g). The ethanolic extract of fresh stem showed the highest antifungal activity (53% inhibition) compared with miconazole (60% inhibition) but the ethanoic extract of dry stem showed no activity. Additionally, all ethanolic extracts, whether for fresh or dry Mentha, have antioxidant activity more than 90% while the antioxidant activity of whole plant volatile oil is equal to 53.33%. This research shows that M. suaveolens L. could be applied to manufacture natural antioxidants, antifungal, and flavoring agents.

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

INTRODUCTION: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance. METHODS: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities. RESULTS: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites. DISCUSSION: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.

Emerging Anthelmintic Resistance in Poultry: Can Ethnopharmacological Approaches Offer a Solution?

Limited pharmacological studies have been conducted on plant species used against poultry helminths. The objective of this study was to provide a basis for plant based anthelmintics as possible alternatives against poultry anthelmintic resistance. The study justified the need for alternative anthelmintics. The study places emphasis on the increasing anthelmintic resistance, mechanism of resistance, and preparational protocols for plant anthelmintics and their associated mechanism of action. Pharmaceutical studies on plants as alternative therapies for the control of helminth parasites have not been fully explored especially in several developing countries. Plants from a broad range of species produce a wide variety of compounds that are potential anthelmintics candidates. Important phenolic acids have been found in Brassica rapa L. and Terminalia avicenniodes Guill. and Perri that affect the cell signaling pathways and gene expression. Benzo (c) phenanthridine and isoquinoline alkaloids are neurotoxic to helminths. Steroidal saponins (polyphyllin D and dioscin) interact with helminthic mitochondrial activity, alter cell membrane permeability, vacuolation and membrane damage. Benzyl isothiocyanate glucosinolates interfere with DNA replication and protein expression, while isoflavones from Acacia oxyphylla cause helminth flaccid paralysis, inhibit energy generation, and affect calcium utilization. Condensed tannins have been shown to cause the death of nematodes and paralysis leading to expulsion from the gastro-intestinal tract. Flavonoids from Chenopodium album L and Mangifera indica L act through the action of phosphodiesterase and Ca2+-ATPase, and flavonoids and tannins have been shown to act synergistically and are complementary to praziquantel. Artemisinins from Artemisia cina O. Berg are known to disrupt mitochondrial ATP production. Terpenoids from Cucurbita moschata L disrupt neurotransmission leading to paralysis as well as disruption of egg hatching. Yeast particle encapsulated terpenes are effective for the control of albendazole-resistant helminths.