Bioactivities of Jojoba Oil Beyond Skincare.

Jojoba oil, which is extracted from jojoba plant seeds that are native to North America, possesses a unique molecular structure and is distinct from other oils. Unlike typical oils, which mostly contain triglycerides, jojoba oil is composed of long monounsaturated esters, affording it exceptional properties and is valuable across cosmetics, chemicals, and pharmaceuticals. While jojoba oil is prevalent in beauty and skincare today, its seeds and oil have ancient roots in folk medicine, used for treating skin and scalp issues, wounds, sore throats, obesity, and even cancer, while enhancing immunity and fostering hair growth. Modern research underscores jojoba oil's pharmacological versatility, demonstrating antioxidant, antidiabetic, anti-acne, anti-inflammatory, antipyretic, and antibacterial properties. Notably, there has been a surge in its utilization in pharmaceuticals, particularly in topical, transdermal, and parenteral formulations. This review provides a comprehensive overview of jojoba oil, encompassing its chemical composition, extraction techniques, health advantages, and pharmaceutical application developments.

PPAR gamma agonistic activity of dillapiole: protective effects against diabetic nephropathy.

Using structural similarity approach we identified dillapiole, a phenylpropanoid, the main component of Piper aduncum L. and Anethum graveolens L. essential oils as potential PPARγ agonist. Molecular docking revealed that dillapiole binds to the active site of PPARγ, similar to pioglitazone binding. In silico ADME studies showed that dillapiole has high water solubility and GI absorption. Dillapiole was also observed to be partial agonist of PPARγ receptors with EC50 of 43.95 µM. In BHK-21 cells cultured under hyperglycaemic conditions, dillapiole administration reduced oxidative stress and prevented decrease in histone H3 acetylation (k9/14) levels. In HFD + STZ induced diabetic mice, dillapiole treatment for 7 days was able to improve renal functions and decrease plasma glucose level to 138.39 ± 12.36 mg/dl along with decreasing total cholesterol (29%), triglycerides (48.8%), LDL (24.7%), and VLDL (65%) levels in serum. These results show that dillapiole is a potential PPARγ-agonist and thus needs to explore further.

Nephro-protective effects of alpha-lipoic acid in type I diabetes.

Type 1 diabetes (T1D) is an insulin-dependent autoimmune condition. Short chain fatty acids (SCFAs) are volatile fatty acids with 1-6 carbon atoms that influence glucose storage in the body and can reduce appetite, potentially decreasing T1D risk. Alpha-lipoic acid (α-LA), a type of SCFA, has previously been used to treat diabetic neuropathy and inflammation due to its antioxidant properties. This study aims to assess α-LA's protective effects against T1D and associated kidney damage in rats induced with streptozotocin. Diabetic rats were treated with α-LA orally for 15 days, resulting in improved blood glucose (56% decrease) and kidney function markers like blood urea nitrogen, creatinine and uric acid. α-LA also showed significant antioxidant effects by decreasing LPO as well as improving activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione-S transferase and alleviated kidney damage caused by diabetes. Docking experiments suggest that α-LA may regulate diabetes-related changes at the epigenetic level through interactions with the SIRT1 protein, indicating its potential as a target for future antidiabetic drug development.

Biological macromolecules-based nanoformulation in improving wound healing and bacterial biofilm-associated infection: A review.

A chronic wound is a serious complication associated with diabetes mellitus and is difficult to heal due to high glucose levels, oxidative stress, and biofilm-associated microbial infection. The structural complexity of microbial biofilm makes it impossible for antibiotics to penetrate the matrix, hence conventional antibiotic therapies became ineffective in clinical settings. This demonstrates an urgent need to find safer alternatives to reduce the prevalence of chronic wound infection associated with microbial biofilm. A novel approach to address these concerns is to inhibit biofilm formation using biological-macromolecule based nano-delivery system. Higher drug loading efficiency, sustained drug release, enhanced drug stability, and improved bioavailability are advantages of employing nano-drug delivery systems to prevent microbial colonization and biofilm formation in chronic wounds. This review covers the pathogenesis, microbial biofilm formation, and immune response to chronic wounds. Furthermore, we also focus on macromolecule-based nanoparticles as wound healing therapies to reduce the increased mortality associated with chronic wound infections.

Therapeutic Management with Repurposing Approaches: A Mystery During COVID-19 Outbreak.

The ubiquitous pandemic that emerged due to COVID-19 affected the whole planet. People all over the globe became vulnerable to the unpredictable emergence of coronavirus. The sudden emergence of respiratory disease in coronavirus infected several patients. This affected human life drastically, from mild symptoms to severe illness, leading to mortality. COVID-19 is an exceptionally communicable disease caused by SARS-CoV-2. According to a genomic study, the viral spike RBD interactions with the host ACE2 protein from several coronavirus strains and the interaction between RBD and ACE2 highlighted the potential change in affinity from the virus causing the COVID-19 outbreak to a progenitor type of SARS-CoV-2. SARS-CoV-2, which could be the principal reservoir, is phylogenetically related to the SARS-like bat virus. Other research works reported that intermediary hosts for the transmission of viruses to humans could include cats, bats, snakes, pigs, ferrets, orangutans, and monkeys. Even with the arrival of vaccines and individuals getting vaccinated and treated with FDA-approved repurposed drugs like Remdesivir, the first and foremost steps aimed towards the possible control and minimization of community transmission of the virus include social distancing, self-realization, and self-health care. In this review paper, we discussed and summarized various approaches and methodologies adopted and proposed by researchers all over the globe to help with the management of this zoonotic outbreak by following repurposed approaches.

Association between obesity, inflammation and insulin resistance: Insights into signaling pathways and therapeutic interventions.

Obesity, a metabolic disorder, is becoming a worldwide epidemic that predominantly increases the risk for various diseases including metabolic inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms that link obesity with other metabolic diseases are not completely understood. In obesity, various inflammatory pathways that cause inflammation in adipose tissue of an obese individual become activated and exacerbate the disease. Obesity-induced low-grade metabolic inflammation perturbates the insulin signaling pathway and leads to insulin resistance. Researchers have identified several pathways that link the impairment of insulin resistance through obesity-induced inflammation like activation of Nuclear factor kappa B (NF-κB), suppressor of cytokine signaling (SOCS) proteins, cJun-N-terminal Kinase (JNK), Wingless-related integration site (Wnt), and Toll-like receptor (TLR) signaling pathways. In this review article, the published studies have been reviewed to identify the potential and influential role of different signaling pathways in the pathogenesis of obesity-induced metabolic inflammation and insulin resistance along with the discussion on potential therapeutic strategies. Therapies targeting these signaling pathways show improvements in metabolic diseases associated with obesity, but require further testing and confirmation through clinical trials.

Guar gum-based nanoformulations: Implications for improving drug delivery.

Poorly soluble drugs are reported to easily degrade in the gastrointestinal tract and contribute in limiting the effect of drug to its targeted site. Oral administration of drug is one of the prominent ways to deliver a drug, although, it experiences barriers like acidic pH, presence of microflora and enzymes in the gastrointestinal tract. Collectively all of these participate in the degradation of drug before it reaches its target site and thus, they impede the sustained effect of drug. A quest of choosing a polymer with good stability profile and releasing the drug to its targeted site is always been a challenge for the scientists worldwide. Many polymers have been reported to prevent the degradation of drug and one such naturally occurring biocompatible polymer is guar gum. Guar gum-based nanoformulations have been extensively used in past decades to achieve controlled drug release which defines its importance. The coating of guar gum over the drug improves the bioavailability of the drug and thus helps in minimizing the risk of drug degradation. This review intends to highlight the beneficial role of guar gum-based nanoformulations to improve drug delivery by ameliorating the bioavailibility.

Pharmacological and Therapeutic Applications of Esculetin.

Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, etc. Free radicals lead to the development of oxidative stress causing inflammation, arthritis, cancer, diabetes, fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver enzymes. For instance, the current treatment modalities used in arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives. Esculetin has an immense antioxidative potential thereby alleviating arthritis, diabetes, malignancies, and hepatic disorders. Structurally, esculetin contains two hydroxyl groups, which enhance its ability to function as an antioxidant by inhibiting oxidative stress in pathological conditions. Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory cytokine production are the main causes of bone and joint deterioration in arthritis, whereas esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-ß-mediated expression and dysfunction of antioxidant enzymes is inhibited by esculetin therapy, thus reducing liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory cytokines, TGF-ß and oxidative stress may be a therapeutic strategy to alleviate arthritis and liver fibrosis.

Diabetic Nephropathy: Pathogenesis to Cure.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disorder (ESRD). It is defined as the increase in urinary albumin excretion (UAE) when no other renal disease is present. DN is categorized into microalbuminuria and macroalbuminuria. Factors like high blood pressure, high blood sugar levels, genetics, oxidative stress, hemodynamic and metabolic changes affect DN. Hyperglycemia causes renal damage through activating protein kinase C (PKC), producing advanced end glycation products (AGEs) and reactive oxygen species (ROS). Growth factors, chemokines, cell adhesion molecules, inflammatory cytokines are found to be elevated in the renal tissues of the diabetic patient. Many different and new diagnostic methods and treatment options are available due to the increase in research efforts and progression in medical science. However, until now, no permanent cure is available. This article aims to explore the mechanism, diagnosis, and therapeutic strategies in current use for increasing the understanding of DN.

Targeting epigenetic regulators for treating diabetic nephropathy.

Diabetes is accompanied by the worsening of kidney functions. The reasons for kidney dysfunction mainly include high blood pressure (BP), high blood sugar levels, and genetic makeup. Vascular complications are the leading cause of the end-stage renal disorder (ESRD) and death of diabetic patients. Epigenetics has emerged as a new area to explain the inheritance of non-mendelian conditions like diabetic kidney diseases. Aberrant post-translational histone modifications (PTHMs), DNA methylation (DNAme), and miRNA constitute major epigenetic mechanisms that progress diabetic nephropathy (DN). Increased blood sugar levels alter PTHMs, DNAme, and miRNA in kidney cells results in aberrant gene expression that causes fibrosis, accumulation of extracellular matrix (ECM), increase in reactive oxygen species (ROS), and renal injuries. Histone acetylation (HAc) and histone deacetylation (HDAC) are the most studied epigenetic modifications with implications in the occurrence of kidney disorders. miRNAs induced by hyperglycemia in renal cells are also responsible for ECM accumulation and dysfunction of the glomerulus. In this review, we highlight the role of epigenetic modifications in DN progression and current strategies employed to ameliorate DN.

Target-based in-silico screening of basil polysaccharides against different epigenetic targets responsible for breast cancer.

PURPOSE: Breast cancer (BC) is one of the leading types of cancer found in women. One of the causes reported for BC is improper regulation of epigenetic modifications. Various epigenetic targets such as histone deacetylases (HDAC) and histone acetyltransferases (HAT) regulate many types of cancer, including BC. Basil is known to possess anti-cancer properties; however, the role of its polysaccharides against different epigenetic targets is still not very clear. Therefore, the molecular docking method is used to find out the binding potential of the BPSs against different epigenetic targets responsible for BC. METHODS: All the basil polysaccharides (BPSs) were screened against the diverse epigenetic targets reported for BC (HDAC1-2, 4-8, and HAT) using molecular docking studies alongwith swissADME studies to check the drug likeliness of the BPSs. RESULTS: It was found that glucosamine ring, glucosamine linear, glucuronic acid linear, rhamnose linear, glucuronic acid ring, galactose ring, mannose, glucose, and xylose were exhibited consistent binding potential against the epigenetic targets (HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HAT,) responsible for BC. CONCLUSION: This is the first report where BPSs were reported against these epigenetic targets. These studies can help to understand the underlying mechanism of BPSs used against epigenetic targets for BC. These results can be further validated experimentally to confirm their potential as a promising inhibitor against the epigenetic targets (HDAC1-2, 4-8, and HAT) having a role in BC.

Polyol pathway and redox balance in diabetes.

Diabetes is a major public health disease that is globally approaching epidemic proportions. One of the major causes of type 2 diabetes is either a defect in insulin secretion or insulin action which is usually caused by a combination of genetic and environmental factors. Not only these factors but others such as deregulation of various pathways, and oxidative stress are also known to trigger the redox imbalance in diabetics. Increasing evidences suggest that there are tight interactions between the development of diabetes and redox imbalance. An alternate pathway of glucose metabolism, the polyol pathway, becomes active in patients with diabetes that disturbs the balance between NADH and NAD+ . The occurrence of such redox imbalance supports other pathways that lead to oxidative damage to DNA, lipids, and proteins and consequently to oxidative stress which further ascend diabetes and its complications. However, the precise mechanism through which oxidative stress regulates diabetes progression remains to be elucidated. The understanding of how antioxidants and oxidants are controlled and impact the generation of oxidative stress and progression of diabetes is essential. The main focus of this review is to provide an overview of redox imbalance caused by oxidative stress through the polyol pathway. Understanding the pathological role of oxidative stress in diabetes will help to design potential therapeutic strategies against diabetes.

Adverse effects of textile dyes on antioxidant enzymes and cholinesterase activities in Drosophila melanogaster (Oregon R+).

The effluents from textile dyeing industry are causing water pollution and may transform into more toxic and carcinogenic chemical species by environmental conditions. Therefore systemic toxicity of textile dyes is major health concern. Hence, this study sought to examine the toxic effect of disperse textile dyes on important systemic enzymes in the larvae of wild type Drosophila melanogaster (Oregon R+). Drosophila larvae were fed with corn-sugar-yeast diets containing two disperse dyes, Disperse blue-124 and Disperse black-9 (1, 10 and 100 mg/mL) for 2 days (48 h) and subsequent the enzymatic estimations were carried out using larval homogenate. In silico molecular docking studies were also performed to analyze the binding interaction of these dyes with acetyl choline esterase enzyme. Disperse black 9 shows more strong binding by occupying a groove and forming one hydrogen bond with Tyr465 of acetyl choline esterase enzyme while Disperse blue-124 shows surface binding without forming any hydrogen bond. Drosophila larvae fed on these dyes exhibited a dose-dependent increase in acetyl choline esterase enzymatic activity (1.8 fold increase with Disperse black-9, 100 mg/mL) while 4.4-folds Disperse blue-124, 100 mg/mL). Both Disperse Blue and Disperse Black dyes altered the activities of antioxidant enzymes Catalase (CAT, increased more than 2.5 fold), Superoxide dismutase (SOD, increased more than two folds) and showed a dose-dependent increase in Xanthine oxidase and lipid peroxidation (LPO) levels (more than 3 folds). Therefore both the disperse dyes were found to dysregulate the activities of antioxidant enzymes which may be the underlying mechanism for their toxic effects.

Vermicomposting with microbial amendment: implications for bioremediation of industrial and agricultural waste.

Improved agricultural practices and rapid industrialization have led to huge waste generation, and the management of this waste is becoming a global concern. The process of vermicomposting has emerged as a method of choice for converting waste into useful manure, with evidence of increase in crop productivity. During vermi-composting, the collective activities of decomposing microorganisms and earthworms lead to the humification of organic/inorganic waste, thereby generating the final product called vermicompost. Different types of industrial wastes such as waste from paper industries, tanneries, sugar mills, and pulp and textile industries have been effectively converted to vermicompost and successfully used to improve plant growth. The vermicompost thus formed was also demonstrated to increase the production of pharmaceutically important plant secondary meta-bolites such as withanolides and polyunsaturated fatty acids. Microbial amendment with different bacterial and fungal strains during vermicomposting further proves to be beneficial by increasing nitrogen content, decomposing organic waste, providing aeration, and stabilizing the vermicompost. These microorganisms after passing through the earthworm's intestine increase in numbers in the vermicast, thus becoming enriched in vermi-compost, which is particularly important for their use as biofertilizers. The precise role of different microbial pretreatments in improving the quality of vermicompost generated from industrial and agricultural waste is, however, not completely understood. To fill this gap in knowledge, the present article aims to review published literature to highlight the potential of microbial amendment during vermicomposting for bioremediation of industrial and agricultural waste. Microbial pre-composting followed by vermicomposting emerges as an eco-friendly and economical approach for managing agricultural and industrial waste.

Epigenetics: key to improve delayed wound healing in type 2 diabetes.

Diabetes-related delayed wound healing is a multifactorial, nuanced, and intertwined complication that causes substantial clinical morbidity. The etiology of diabetes and its related microvascular complications is affected by genes, diet, and lifestyle factors. Epigenetic modifications such as DNA methylation, histone modifications, and post-transcriptional RNA regulation (microRNAs) are subsequently recognized as key facilitators of the complicated interaction between genes and the environment. Current research suggests that diabetes-persuaded dysfunction of epigenetic pathways, which results in changed expression of genes in target cells and cause diabetes-related complications including cardiomyopathy, nephropathy, retinopathy, delayed wound healing, etc., which are foremost drivers to diabetes-related adverse outcomes. In this paper, we discuss the role of epigenetic mechanisms in controlling tissue repair, angiogenesis, and expression of growth factors, as well as recent findings that show the alteration of epigenetic events during diabetic wound healing.

p-Coumaric acid attenuates high-fat diet-induced oxidative stress and nephropathy in diabetic rats.

The prevalence of persistent hyperglycaemia during diabetes, impair antioxidant defence system and generate reactive oxygen species, which majorly contribute to its progression and associated complications. Phytochemicals were suggested to scavenge-free radicals and exert antioxidant effects required to improve insulin sensitivity and reduce the occurrence of diabetes-associated complications. We hypothesise that a phenolic phytochemical p-coumaric can reduce diabetes-induced oxidative stress and improve diabetes-associated nephropathy in rats. The aim of this study is to analyse the protective effects of p-coumaric acid against diabetes-induced oxidative stress and nephropathy in high-fat diet-induced diabetic rats. The oral feeding of p-coumaric acid (20 mg/kg for 12 weeks) was found to significantly decrease the elevated levels of blood glucose in high-fat diet-induced type 2 diabetic rats. p-Coumaric acid treatment also decreases the kidney weight whilst increasing the total body weight of diabetic rats. Furthermore whilst evaluation of the different renal functioning tests, p-coumaric acid significantly improves histopathological changes and the levels of urea, creatinine and uric acid in serum of diabetic rats, which was otherwise elevated under diabetic conditions. Our results also highlight that p-coumaric acid is an efficient compound with antioxidant properties and improves the diabetes-induced change in lipid peroxidation and activities of antioxidant enzymes: catalase, glutathione-S-transferase and superoxide dismutase. p-Coumaric acid thus possesses the potential to prevent diabetic nephropathy by reducing oxidative stress and can thus serve as a potential drug target for pharmaceutical companies.

Focused review on dual inhibition of quorum sensing and efflux pumps: A potential way to combat multi drug resistant Staphylococcus aureus infections.

Staphylococcus aureus is a common cause of skin infections, food poisoning and severe life-threatening infections. Methicillin-Resistant Staphylococcus aureus (MRSA) is known to cause chronic nosocomial infections by virtue of its multidrug resistance and biofilm formation mechanisms. The antimicrobial resistance owned by S. aureus is primarily due to efflux pumps and formation of microbial biofilms. These drug resistant, sessile and densely packed microbial communities possess various mechanisms including quorum sensing and drug efflux. Quorum sensing is a cooperative physiological process which is used by bacterial cells for social interaction and signal transduction in biofilm formation whereas efflux of drugs is derived by efflux pumps. Apart from their significant role in multidrug resistance, efflux pumps also contribute to transporting cell signalling molecules and due to their occurrence; we face the frightening possibility that we will enter the pre-antibiotic era soon. Compounds that modulate efflux pumps are also known as efflux pump inhibitors (EPI's) that act in a synergistic manner and potentiate the antibiotics efficacy which has been considered as a promising approach to encounter bacterial resistance. EPIs inhibit the mechanism of drug efflux s as well as transport of quorum sensing signalling molecules which are the supreme contributors of miscellaneous virulence factors. This review presents an accomplishments of the recent investigations allied to efflux pump inhibitors against S. aureus and also focus on related correspondence between quorum sensing system and efflux pump inhibitors in terms of S. aureus and MRSA biofilms that may open a new avenue for controlling MRSA infections.

Immunomodulation and immunotherapeutics of COVID-19.

Severe acute respiratory syndrome coronavirus-2 causes coronavirus disease 2019, a pandemic which was originated from Wuhan city of China. The pandemic has affected millions of people worldwide. The pathogenesis of SARS-CoV-2 is characterized by a cytokine storm in the blood (cytokinemia) and tissues, especially the lungs. One of the major repercussions of this inflammatory process is the endothelial injury-causing intestinal bleeding, coagulopathy, and thromboembolism which result in various sudden and unexpected post-COVID complications including kidney failure, myocardial infarction, or multiorgan failure. In this review, we have summarized the immune responses, biochemical changes, and inflammatory responses in the human body after infection with the SARS-CoV-2 virus. The increased amount of inflammatory cytokines, chemokines, and involvement of complement proteins in inflammatory reaction increase the risk of occurrence of disease.

In silico, in-vitro and in vivo screening of biological activities of citral.

Citral, one of the main components of lemongrass oil (65-85%), is known to possess various medicinal properties like enhancing skin health and vision-improvement. It also acts as flavoring agent, used in perfumes and skin care products. The objective of this work was to elucidate the biological properties of citral at molecular level using an integrated in silico, in vitro and in vivo approaches. To elucidate this in silico molecular docking studies were performed with in vitro validation by DPPH scavenging activity, MTT assays, enzymatic assays and Chorio Allantoic Membrane (CAM) assay. The in silico analysis demonstrated the potential binding of citral with PPARγ ligand binding domain and vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2). Citral is already a proven anti-oxidant which is further confirmed by increased DPPH inhibition with increased citral concentration (IC50: 6.9 ± 1.68 µg/ml, p < 0.05). The results demonstrated that citral protect yeast cells from cytotoxic effects of hydrogen peroxide and also increase the activities of antioxidant enzymes like GST, SOD and LPO. It was also demonstrated to be cytotoxic to cancerous HeLa cells (IC50: 3.9 ± 0.38 µM, p < 0.01) and was found anti-angiogenic by CAM assay. This study highlights many important pharmaceutical properties of citral which can be explored further to increase its industrial applications.

Chemical Properties and Therapeutic Potential of Citral, a Monoterpene Isolated from Lemongrass.

BACKGROUND: Citral is one of the main components of lemongrass oil present at a concentration of 65-85% approximately and is generally separated by steam refining. It is an important component in the manufacturing of scents, citrus chemicals, cosmetics, food and pharmaceutical products. OBJECTIVES: This article aims at reviewing the published literature to highlight the metabolism, extraction strategies and therapeutic significance of citral for improving the scope of its application in the food and pharma industry. DISCUSSIONS: Apart from steam refining, there are other techniques like solvent extraction, supercritical fluid extraction and ultrasonication by which citral can be extracted and the method of extraction defines its quality. It is an unstable molecule and undergoes rapid deterioration on exposure to air. Citral is biosynthesized by the plants through the 5 carbon precursor isopentenyl diphosphate (IPP) units utilizing two diverse biochemical pathways, acetate- mevalonate (acetate- MVA) pathway or 2C-methylerythritol-4-phosphate (MEP). Orally Citral was absolutely digested in the gastrointestinal tract and its metabolism leads to the discharge of metabolites which include a number of acids and a biliary glucuronide. There is no scientific evidence about the long term bioavailability of citral in the body and it has no adverse effect on tissue related to its accumulation and delayed excretion. Citral exhibits various important therapeutic properties like antimicrobial, antioxidant, anticancer, anti-diabetic and anti-inflammatory. CONCLUSION: Citral is a potent biomolecule with various important biological activities and therapeutic implications. Strategies are required to increase the stability of citral which could increase its applications.