Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies.

Diabetes mellitus is a prevalent cause of mortality worldwide and can lead to several secondary issues, including DWs, which are caused by hyperglycemia, diabetic neuropathy, anemia, and ischemia. Roughly 15% of diabetic patient's experience complications related to DWs, with 25% at risk of lower limb amputations. A conventional management protocol is currently used for treating diabetic foot syndrome, which involves therapy using various substances, such as bFGF, pDGF, VEGF, EGF, IGF-I, TGF-ß, skin substitutes, cytokine stimulators, cytokine inhibitors, MMPs inhibitors, gene and stem cell therapies, ECM, and angiogenesis stimulators. The protocol also includes wound cleaning, laser therapy, antibiotics, skin substitutes, HOTC therapy, and removing dead tissue. It has been observed that treatment with numerous plants and their active constituents, including Globularia Arabica, Rhus coriaria L., Neolamarckia cadamba, Olea europaea, Salvia kronenburgii, Moringa oleifera, Syzygium aromaticum, Combretum molle, and Myrtus communis, has been found to promote wound healing, reduce inflammation, stimulate angiogenesis, and cytokines production, increase growth factors production, promote keratinocyte production, and encourage fibroblast proliferation. These therapies may also reduce the need for amputations. However, there is still limited information on how to prevent and manage DWs, and further research is needed to fully understand the role of alternative treatments in managing complications of DWs. The conventional management protocol for treating diabetic foot syndrome can be expensive and may cause adverse side effects. Alternative therapies, such as medicinal plants and green synthesis of nano-formulations, may provide efficient and affordable treatments for DWs.

A review of botany, traditional applications, phytochemistry, pharmacological applications, and toxicology of Rubus ellipticus Smith fruits.

Rubus ellipticus Smith. (Family Rosaceae), often known as the yellow Himalayan raspberry (Yellow Hissar), is one of the most widely used edible fruits in Indian folk medicinal systems. The current review aims to identify the gap between research and existing applications of this fruit to help scientists explore the current trends and opportunities for future development. Fruits of R. ellipticus are the source of several classes of compounds. Fruits of R. ellipticus are also rich in nutrients such as carbohydrates, vitamins, and minerals. It has been shown to have significant medical value in a variety of studies, including as an anti-diabetic, nephroprotective, anti-inflammatory, analgesic, antipyretic, antitumor, wound healing, antifertility, oviposition deterrent, antibacterial, and antioxidant. Fruits of R. ellipticus have been the subject of several in vitro and in vivo investigations, all of which have corroborated their wide range of biological activities and demonstrated their potential for the identification of new therapeutic candidates and the development of innovative herbal food supplements. Additional mechanism-based pharmacological evaluation and clinical research should provide an adequate scientific basis for the traditional usage of R. ellipticus fruits, which is currently not sufficiently supported by the available research on its active components and molecular mechanisms.

Synergistic antibacterial activity of Phyllanthus emblica fruits and its phytocompounds with ampicillin: a computational and experimental study.

Phyllanthus emblica L. (syn. Emblica officinalis), popularly known as amla, Indian gooseberry, or the King of Rasyana, is a member of Phyllanthaceae family and is traditionally used in Ayurveda as an immunity booster. The present study aimed to investigate the synergistic interaction of Phyllanthus emblica (FPE) fruits and its selected phytocompounds with ampicillin against selected bacteria. Further, an in silico technique was used to find if major phytocompounds of FPE could bind to proteins responsible for antibiotic resistance in bacterial pathogens and enhance the bioactivity of ampicillin. FPE and all the selected phytocompounds were found to have synergistic antibacterial activity with ampicillin against tested bacteria in different combinations. However, ellagic acid and quercetin interactions with ampicillin resulted in maximum bioactivity enhancement of 32-128 folds and 16-277 folds, respectively. In silico analysis revealed strong ellagic acid, quercetin, and rutin binding with penicillin-binding protein (PBP-) 3, further supported by MD simulations. Ellagic acid and quercetin also fulfill Lipinski's rule, showing similar toxicity characteristics to ampicillin. FPE showed synergistic interaction with ampicillin, possibly due to the presence of phytocompounds such as gallic acid, ellagic acid, quercetin, and rutin. Molecular docking and MD simulations showed the strong interaction of ellagic acid and quercetin with PBP-3 protein. Therefore, these compounds can be explored as potential non-toxic drug candidates to combat bacterial antimicrobial resistance.

Effects of Apple Polyphenols and Taurine on Growth Performance, Tissue Morphology, and Lipid and Glucose Metabolism in Rice Field Eel (Monopterus albus) Fed High Oxidized Fish Oil.

The aim of this trial was to investigate the effects of apple polyphenols (AP) and taurine (TA) on the growth performance, tissue morphology, and lipid and glucose metabolism in rice field eel fed diets with high oxidized fish oil (OFO). A 10-week feeding experiment was conducted using juveniles (initial body weight 16.66 ± 0.02 g) fed five different diets. Three diets were formulated with various levels of OFO at 9.5, 600, and 800 meq·kg-1 and named as Control, POV600, and POV800 diet, respectively. The other two diets were POV600 and POV800 supplemented with 0.5% AP and 0.2% TA, respectively. Compared to the Control group, only the eels fed POV800 exhibited an increase in weight gain and specific growth rate along with a reduction in feed conversion ratio. AP and TA did not affect growth performance; juveniles fed AP, however, showed a decrease in liver weight. Both POV600 and POV800 decreased nuclei number and increased vacuoles size in the liver. POV800 damaged the intestinal structure integrity and reduced goblet cells number. AP repaired the liver damage on nuclei number and vacuoles size in fish fed with POV600 diet, while TA mitigated intestinal histopathological damage on intact structure and goblet cells number. The mRNA expression level of liver ampkα in fish fed AP was upregulated, while dietary TA upregulated the mRNA expression levels of liver ampkα and accα. In the muscle, POV600 downregulated mRNA expression levels of accα, cpt1, and lipin, whereas POV800 upregulated mRNA expression levels of accα, pparα, and lipin. Dietary AP and TA could counteract the effects of POV600 and POV800 diet on muscle lipid metabolism. Both POV600 and POV800 diets upregulated mRNA expression levels of liver pck1 and gsk3α. AP and TA both downregulated mRNA expression level of liver pck1, while only TA downregulated the expression of liver gsk3α. AP increased the mRNA expression level of gsk3α in muscle. In summary, inclusion of AP and TA did not affect growth performance but showed a potential to alleviate liver or intestinal damages induced by a high OFO diet. Dietary AP and TA were also found to regulate mRNA expression of genes related to lipid and glucose metabolism.

A comprehensive review on the phytochemistry, pharmacological properties, and in vitro propagation of an endemic medicinal orchid, Dactylorhiza hatagirea.

Dactylorhiza hatagirea (D. Don) Soo, also known as Himalayan Marsh Orchid or Salam Panja, belongs to the Orchidaceae family. It is found in sub-alpine to alpine regions at 2500-5000 m above sea level. The present review aims to provide a comprehensive overview of the botany, phytochemistry, medicinal uses, toxicity, and conservation status of D. hatagirea and to find the research gaps to promote progress in studies of this orchid. Secondary metabolites, including alkaloids, terpenoids, flavonoids, phenolics, and saponins, were reported from the aerial and underground parts of this medicinal orchid. Several phytocompounds, such as dactylorhins A, B, C, D, and E and dactylose A and B, were isolated from the dried roots of D. hatagirea. A wide range of in vitro and in vivo assays was used to assess the biological properties of D. hatagirea, such as antirheumatic, anti-inflammatory, antiviral, diuretic, neuroprotective, antioxidant, wound healing, hypoglycemic, antitumor, antimicrobial, antiviral, and anticancer activities. It was also reported to boost testosterone levels, improving sexual desire and arousal. Due to overexploitation and a restricted habitat range, this essential medicinal plant has reached the extinction stage; therefore, a conservation-friendly harvesting approach is needed for this medicinal herb. In vitro techniques such as micropropagation, synthetic seed generation, and hairy root technology can contribute to its conservation. This review provides comprehensive insights into the botanical features, traditional uses, phytochemicals, pharmacological importance, and toxicity evaluation of this medicinal orchid. This review also provides detailed information on the conservation status of D. hatagirea and strategies to overcome the exploitation of this orchid.

Genetics, Nutrition, and Health: A New Frontier in Disease Prevention.

The field of nutrition research has traditionally focused on the effects of macronutrients and micronutrients on the body. However, it has become evident that individuals have unique genetic makeups that influence their response to food. Nutritional genomics, which includes nutrigenetics and nutrigenomics, explores the interaction between an individual's genetic makeup, diet, and health outcomes. Nutrigenetics studies the impact of genetic variation on an individual's response to dietary nutrients, while nutrigenomics investigates how dietary components affect gene regulation and expression. These disciplines seek to understand the impact of diet on the genome, transcriptome, proteome, and metabolome. It provides insights into the mechanisms underlying the effect of diet on gene expression. Nutrients can cause the modification of genetic expression through epigenetic changes, such as DNA methylation and histone modifications. The aim of nutrigenomics is to create personalized diets based on the unique metabolic profile of an individual, gut microbiome, and genetic makeup to prevent diseases and promote health. Nutrigenomics has the potential to revolutionize the field of nutrition by combining the practicality of personalized nutrition with knowledge of genetic factors underlying health and disease. Thus, nutrigenomics offers a promising approach to improving health outcomes (in terms of disease prevention) through personalized nutrition strategies based on an individual's genetic and metabolic characteristics.

Genetic differences among individuals affect the metabolism, gene regulation, and sensitivity of disease in response to diet therefore traditional nutrition research expands to integrate the influence of genetics on the dietary response of an individual.Nutritional genomics which includes the reciprocal and complementary field of nutrigenetics and nutrigenomics, studies the interactions between gene and dietary components.Nutrigenetics studies the genetic effect on the metabolism of nutrients while Nutrigenomics explores the impact of nutrients on genetic expression thus shaping personalized dietary requirements.A personalized dietary approach based on comprehensive genomic profiling (genomics, proteomics, metabolomics, transcriptomics) can help to promote health and prevent illness.

Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives.

BACKGROUND: The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE: To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN: A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS: An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS: Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS: The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.

An Immobilized Form of a Blend of Essential Oils Improves the Density of Beneficial Bacteria, in Addition to Suppressing Pathogens in the Gut and Also Improves the Performance of Chicken Breeding.

Antimicrobial growth promoters (AGP) are used in chicken production to suppress pathogens in the gut and improve performance, but such products tend to suppress beneficial bacteria while favoring the development and spread of antimicrobial resistance. A green alternative to AGP with the ability to suppress pathogens, but with an additional ability to spare beneficial gut bacteria and improve breeding performance is urgently required. We investigated the effect of supplementation of a blend of select essential oils (cinnamon oil, carvacrol, and thyme oil, henceforth referred to as EO; at two doses: 200 g/t and 400 g/t feed) exhibiting an ability to spare Lactobacillus while exhibiting strong E. coli inhibition ability under in vitro tests and immobilized in a sunflower oil and calcium alginate matrix, to broiler chickens and compared the effects with those of a probiotic yeast (Y), an AGP virginiamycin (V), and a negative control (C). qPCR analysis of metagenomic DNA from the gut content of experimental chickens indicated a significantly (p < 0.05) lower density of E. coli in the EO groups as compared to other groups. Amplicon sequence data of the gut microbiome indicated that all the additives had specific significant effects (DESeq2) on the gut microbiome, such as enrichment of uncultured Clostridia in the V and Y groups and uncultured Ruminococcaceae in the EO groups, as compared to the control. LEfSe analysis of the sequence data indicated a high abundance of beneficial bacteria Ruminococcaceae in the EO groups, Faecalibacterium in the Y group, and Blautia in the V group. Supplementation of the immobilized EO at the dose rate of 400 g/ton feed improved body weight gain (by 64 g/bird), feed efficiency (by 5 points), and cellular immunity (skin thickness response to phytoheamagglutinin lectin from Phaseolus vulgaris by 58%) significantly (p < 0.05), whereas neither yeast nor virginiamycin showed a significant effect on performance parameters. Expression of genes associated with gut barrier and immunity function such as CLAUDIN1, IL6, IFNG, TLR2A, and NOD1 were significantly higher in the EO groups. This study showed that the encapsulated EO mixture can improve the density of beneficial microbes in the gut significantly, with concomitant suppression of potential pathogens such as E.coli and improved performance and immunity, and hence, has a high potential to be used as an effective alternative to AGP in poultry.

Tomato seed oil enriched mayonnaise: structural, rheological, and biochemical characterization.

Two types of mayonnaise viz. eggless and egg based were prepared by substituting refined soybean oil by tomato seed oil (TSO) at varying concentrations (0-30%). Aim of the study was to utilise the potential of TSO in replaced of refined oil. With respect to oil particle distribution pattern in both types of mayonnaise, higher specific surface area (Dmean ~ 11.49 µm) and homogenous distribution of oil droplets was noted in egg-based mayonnaise. Rheological behavior depicted shear thinning properties in all types of mayonnaise with low viscosity (1.08 Pa s and 2.29 Pa s) being exhibited by tomato seed oil (TSO) incorporated mayonnaise. Nutritionally, significant increase of 65.5 and 26% in lycopene content while 29 and 34% increase in carotenoid content was noted upon incorporation of TSO in eggless and egg-based mayonnaise. Good storage and oxidative stability were demonstrated by TSO egg-based and eggless mayonnaise in terms of acid value and free fatty acids, also the peroxide value was also found lower than their respective control at the end of storage. Overall, tomato seed oil could be used as a non-conventional source of oil for such food applications owing to its close proximity with other vegetable oils and better nutritional profile like dominance of linoleic fatty acid i.e., 54.23% assayed via gas chromatography. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05771-7.

Phytochemical Analysis, In Vitro Biological Activities, and Computer-Aided Analysis of Potentilla nepalensis Hook Compounds as Potential Melanoma Inhibitors Based on Molecular Docking, MD Simulations, and ADMET.

Potentilla nepalensis Hook is a perennial Himalayan medicinal herb of the Rosaceae family. The present study aimed to evaluate biological activities such as the antioxidant, antibacterial, and anticancer activities of roots and shoots of P. nepalensis and its synergistic antibacterial activity with antibacterial drugs. Folin-Ciocalteau and aluminium chloride methods were used for the calculation of total phenolic (TPC) and flavonoid content (TFC). A DPPH radical scavenging assay and broth dilution method were used for the determination of the antioxidant and antibacterial activity of the root and shoot extracts of P. nepalensis. Cytotoxic activity was determined using a colorimetric MTT assay. Further, phytochemical characterization of the root and shoot extracts was performed using the Gas chromatography-mass spectrophotometry (GC-MS) method. The TPC and TFC were found to be higher in the methanolic root extract of P. nepalensis. The methanolic shoot extract of P. nepalensis showed good antioxidant activity, while then-hexane root extract of P. nepalensis showed strong cytotoxic activity against tested SK-MEL-28 cells. Subsequently, in silico molecular docking studies of the identified bioactive compounds predicted potential anticancer properties. This study can lead to the production of new herbal medicines for various diseases employing P. nepalensis, leading to the creation of new medications.

Therapeutic potential and industrial applications of Terminalia arjuna bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia arjuna (Roxb. ex DC.) Wight & Arnot (Combretaceae) is one of the most frequently used medicinal trees in Indian traditional medicinal systems. It is used for the treatment of a variety of diseases including cardiovascular disorders. AIM OF THE STUDY: The purpose of this review was to provide a comprehensive overview of the phytochemistry, medicinal uses, toxicity, and industrial applications of T. arjuna bark (BTA), as well as to identify gaps in research and applications of this important tree. It also aimed to analyze trends and future research paths to utilize the full potential of this tree. MATERIALS AND METHODS: Extensive bibliographic research on the T. arjuna tree was carried out using scientific research engines and databases such as Google Scholar, PubMed, and Web of Science, covering all relevant English-language articles. The database "World Flora Online (WFO)" (http://www.worldfloraonline.org) was used to confirm plant taxonomy. RESULTS: To date, BTA has been traditionally employed for several disorders such as snakebites, scorpion stings, gleets, earaches, dysentery, sexual disorders, and urinary tract infections along with the cardioprotective activity. About 38 phytocompounds were identified from BTA and were classified as triterpenoids, tannins, flavonoids, and glycosides. A wide range of in vitro and in vivo pharmacological effects of BTA were reported such as anti-cancer, antimicrobial, antiviral, anti-inflammatory, antioxidant, hepatoprotective, anti-allergic, anti-diabetic, and wound healing activities. The oral administration of BTA (500 mg/kg) per day did not result in any toxicity in humans. The in vivo acute and sub-acute toxicity analysis of the methanol extract of BTA and one of its major compounds, 7-methyl gallate, did not produce any adverse effects up to a dose of 1000 mg/kg. CONCLUSIONS: This comprehensive review highlights various aspects of traditional knowledge, phytochemicals, and pharmacological significance of BTA. The review covered safety information on employing BTA in pharmaceutical dosage forms. Despite its long history of medicinal benefit, more studies are needed to understand the molecular mechanisms, structure-activity relationship, and potential synergistic and antagonistic effects of its phytocompounds, drug administration, drug-drug interactions, and toxicological effects.

Multitarget Potential of Phytochemicals from Traditional Medicinal Tree, Terminalia arjuna (Roxb. ex DC.) Wight & Arnot as Potential Medicaments for Cardiovascular Disease: An In-Silico Approach.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Terminalia arjuna (Roxb. ex DC.) Wight & Arnot of the Combretaceae family is one of the most frequently approved and utilized medicinal trees in the traditional medicinal system, which was used for the treatment of a variety of diseases, including cardiovascular disorders. The present study aims to identify phytochemicals from T. arjuna, that do not exhibit any toxicity and have significant cardioprotective activity using an in-silico technique. Four different cardiovascular proteins, namely human angiotensin receptor (PDB ID: 4YAY), P38 mitogen-activated protein kinase (MAPK, PDB ID: 4DLI), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-Co A) reductase (PDB ID: 1HW9), and human C-reactive protein (PDB ID: 1B09), were used as target proteins to identify potential inhibitors using a virtual screening of the phytochemicals in T. arjuna revealed casuarinin as a potential inhibitor of all selected target proteins with strong binding energy. Furthermore, MD simulations for a 100 ns time scale also revealed that most of the key protein contacts of all target proteins were retained throughout the simulation trajectories. Binding free energy calculations using the MM-GBSA approach also support a strong inhibitory effect of casuarinin on target proteins. Casuarinin's effective binding to these proteins lays the groundwork for the development of broad-spectrum drugs as well as the understanding of the underlying mechanism against cardiovascular diseases through in vivo and clinical studies.

Dietary supplementation of ß-1, 3-glucan improves the intestinal health of white shrimp (Litopenaeus vannamei) by modulating intestinal microbiota and inhibiting inflammatory response.

The phenomenon of intestinal dysfunction is widely observed in white shrimp (Litopenaeus vannamei) culture, and ß-1,3-glucan has been confirmed to be beneficial in intestinal health with a lack understanding of its underlying mechanism. Proteobacteria, Firmicutes, and Actinobacteria served as the predominant phyla inhabiting the intestine of white shrimp, whilst a significant variation in their proportion was recorded in shrimp fed with basal and ß-1,3-glucan supplementation diets in this study. Dietary supplementation of ß-1,3-glucan could dramatically increase the microbial diversity and affect microbial composition, concurrent with a notable reduction in the ratio of opportunistic pathogen Aeromonas, gram-negative microbes, from Gammaproteobacteria compared to the basal diet group. The benefits for microbial diversity and composition by ß-1,3-glucan improved the homeostasis of intestinal microbiota through the increase of specialists' number and inhibition of microbial competition caused by Aeromonas in ecological networks; afterward, the inhibition of Aeromonas by ß-1,3-glucan diet dramatically suppressed microbial metabolism related to lipopolysaccharide biosynthesis, followed by a conspicuous decrease in the intestinal inflammatory response. The improvement of intestinal health referred to the elevation in intestinal immune and antioxidant capacity, ultimately contributing to the growth of shrimp fed ß-1,3-glucan. These results suggested that ß-1,3-glucan supplementation improved the intestinal health of white shrimp through the modulation of intestinal microbiota homeostasis, the suppression of intestinal inflammatory response, and the elevation of immune and antioxidant capacity, and subsequently promoted the growth of white shrimp.

Studies on the morphology, phylogeny, and bioremediation potential of Penicillium citrinum and Paecilomyces variotii (Eurotiales) from oil-contaminated areas.

Crude oil pollution is one of the most arduous issues to address, as it is hazardous to both public health and the environment. The discovery of novel biosurfactants-producing fungi and bacteria is in high demand due to their excellent properties and wide range of applications. The aim of this research is to isolate a powerful biosurfactant-producing fungus from the crude oil site near Barauni oil refinery in Bihar, India. Standard protocols were used to collect samples from the site. An integrative taxonomic approach was used, which included morphological, molecular, and phylogenetic analysis. The use of plating samples on Bushnell-Hass (BH) media aided in the isolation of a fungal strain from an enrichment culture. Two fungal strains isolated from contaminated soils, Penicillium citrinum and Paecilomyces variotti, showed potent oil degrading activity in a single culture. For preliminary biosurfactants screening, drop collapse assays, oil spreading, and emulsification activity tests were used. The results showed that the cultures performed well in the screening test and were further evaluated for degradation capacity. Different treatment periods (0, 3, 6, 9, 12, and 15 days) were used to observe degradation in single cultures. A steady drop in pH, an alteration in optical density and an increase in carbon dioxide release showed the ability of fungal strain to degrade the crude oil in a single culture. Fungi mycelia provide a larger surface area for absorption and degradation of the pollutants in contaminated environment. They produce extracellular enzymes to degrade the oil, and at the same time absorb and utilise carbon, allowing them to remove toxic substances from the oil. Thus, they could be candidates for bioremediation of a hydrocarbon-contaminated site.

Molecular insights into the interaction of eighteen different variants of SARS-CoV-2 spike proteins with sixteen therapeutically important phytocompounds: in silico approach.

SARS-CoV-2 has mutated many times among different populations. We analyzed wild-type spike protein and 18 different variants of SARS-CoV-2 spike protein known until the beginning of 2022 (alpha, beta, B.1.429, B.1.616, B.1.620, B.1.617.3, C.1.2, delta, epsilon, eta, gamma, iota, kappa, lambda, mu, omicron, theta, and zeta) for their interaction with 16 phytocompounds and remdesivir, resulting into 425 combinations. The largest number of mutations has been reported in the omicron followed by delta variant. However, the virulence of the delta variant has been reported higher as compared to omicron. Mutations at a few locations (D215G, K417N, E484K, N501Y, D614G, and P681H) were common in most of the variants. 3 D structures of all the 18 spike proteins were created using SWISS-MODEL to test the binding affinities with caffeine theophylline, emodin, vitexin, berberine, curcumin, piperine, quercetin, artemisinin, carvacrol, capsaicin, tetrahydrocannabinol, cannabidiol, α- pinene, ß- pinene and gingerol. Phytocompounds and mutant variants were prepared using AutoDock 4.2.6 software. Binding affinities of the selected phytocompounds with the different mutant spike proteins were achieved using AutoDock Vina. Out of all combinations investigated, the best binding affinities were observed with 3 variants of SAR-CoV-2 with 5 phytocompounds along with remdesivir. The range of best binding energies varied from -9.1 to -8.0 kcal/mol. Further, MD simulation was done for selected 9 phytocompound-spike mutant complexes for analyzing the stability of interactions for 100 ns. ADMET studies via ProTox-II and SwissADME displayed that phytocompounds are safe and less toxic in comparison to remdesivir.Communicated by Ramaswamy H. Sarma.

A comprehensive review on traditional applications, phytochemistry, pharmacology, and toxicology of Thymus serpyllum.

Thymus serpyllum L. from the Lamiaceae family is an underexplored perennial medicinal shrub with traditional usage in treating respiratory and gastrointestinal issues in the upper foothills of India. This review aims to provide a comprehensive assessment of current knowledge concerning the traditional uses, phytochemistry, and pharmacology of T. serpyllum. The primary objective is to collect updated information on this plant and encourage further in vivo and in vitro research to validate local claims. Notably, the essential oil derived from T. serpyllum has gained significant attention as a plant-derived product due to its diverse pharmacological properties, including antioxidative, antimicrobial, anti-inflammatory, and anticancer activities. Ethnomedicinal research revealed a vast scope of T. serpyllum in developing new drugs to address numerous health sector challenges. While T. serpyllum has been used widely, pharmacological studies are not enough. Most studies are either in vivo or in vitro. More studies are required to assess these medicinal claims through well-planned pharmacological experiments. This review will provide the groundwork for future research. While T. serpyllum has been put to considerable conventional use, pharmacological studies are insufficient; most studies are either in vivo or in vitro. More compound isolation, comprehensive pharmacological analysis, and exploration of food applications are vital areas to investigate.

A Review of Medicinal Plants of the Himalayas with Anti-Proliferative Activity for the Treatment of Various Cancers.

Cancer is a serious and significantly progressive disease. Next to cardiovascular disease, cancer has become the most common cause of mortality in the entire world. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy and radiation therapy. Traditional medicine has a long history that begins with the hunt for botanicals to heal various diseases, including cancer. In the traditional medicinal system, several plants used to treat diseases have many bioactive compounds with curative capability, thereby also helping in disease prevention. Plants also significantly contributed to the modern pharmaceutical industry throughout the world. In the present review, we have listed 33 medicinal plants with active and significant anticancer activity, as well as their anticancer compounds. This article will provide a basic set of information for researchers interested in developing a safe and nontoxic active medicinal plant-based treatment for cancer. The research will give a scientific foundation for the traditional usage of these medicinal herbs to treat cancer.

Process Optimization for the Development of Nutritionally Enhanced Nuggets using Ficus geniculata: A Nutritional Approach.

Ficus geniculata (FG) is one of the underutilized fig species in India and throughout the world. However, the different parts of the plant have numerous phytochemicals and have the potential to boom the functional food as well as the pharmaceutical food industry. The plant is still unexplored and needs the attention of researchers and industrialists for its value addition. Therefore, in the present investigation, different parts (shoot, leaves and bark) of FG were exploited and leaves were selected based on physicochemical and phytochemical analysis for nugget supplementation. The FG leaves powder incorporated nuggets were prepared using different variables: FG (0 to 50%), salt (0.07 to 0.92%), and black pepper (0.079 to 0.92%) along with black gram as filler to make it 100%. The optimum conditions for the production of supplemented nuggets were having 0.82 desirability. The Fourier transform infrared spectroscopy (FTIR) also confirms the retention of bioactive compounds in the nuggets. No remarkable clustering was observed, which indicating the significant (p ≤ 0.05) effect of all the variables on the quality attributes of the supplement nuggets. Thus the developed conditions will be useful for the nugget industry and also may be a good alternative to the vegetarian people.

Different dietary combinations of high/low starch and fat with or without bile acid supplementation on growth, liver histopathology, gene expression and fatty acid composition of largemouth bass, Micropterus salmoides.

High dietary levels of fat and/or starch can lower the growth and cause extensive liver inflammation that is linked to mortalities in largemouth bass, Micropterus salmoides. However, bile acids (BA) may mitigate these adverse effects. In a 2 × 2 × 2 factorial feeding trial, M. salmoides juveniles were fed different combinations of dietary high (HF), low fat (LF), high (HS) or low starch (LS) levels with or without BA supplementations at 1% for 8 weeks. A total of 8 isonitrogenous diets were formulated to include, HF/LS, HF/HS, LF/HS, LF/LS, HF/LS-BA, HF/HS-BA, LF/HS-BA and LF/LS-BA. Survival, growth performance, feeding efficiency, whole-body proximate composition, muscle/liver fatty acid composition, hepatic expression of growth regulator (GH/IGF1 axis), lipid metabolism (fatty acid synthase 'FASN' and cholesterol 7 alpha-hydroxylase 'CYP7A1') and antioxidant capacity (superoxide dismutase 'SOD') genes as well as liver histopathology were assessed. Results showed that among diets without BA, there was no significant effect on growth or feeding efficiency, but when BA was included this led to more variable effects including significantly higher weight gain in the LF/HS-BA group compared to all others fed BA. The HF, HS or their combination led to extensive hepatic inflammation, but BA appeared to partially mitigate this in the LF/HS group (i.e. LF/HS-BA). No abnormal liver histopathology was observed in the LF/LS and LF/LS-BA treatments. Muscle 22:6n-3 was significantly higher in the HF/LS and HF/HS-BA groups compared to those fed the HF/HS or LF/LS diets. Dietary fat had a significant effect on the moisture, crude lipid, and caloric content of M. salmoides. Hepatic expression of IGF-I and CYP7A1 were differentially modulated under different treatments. Overall, these results show that BA can alleviate some liver inflammation caused by high dietary starch; however the LF/LS diets led to a better balance between growth performance and liver health.