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Abstract Withania somnifera (Ashwagandha) is one of the most renowned and revered medicinal plants in the Indian Ayurvedic system of medicine. Ashwagandha Rasayanas (tonics), capsules, tablets, and powdered herbs (churna) have been used for curing a wide variety of ailments, including reproductive problems, and for improving fertility in men and women as well as erectile dysfunction (ED) in men. Iron accumulation in reproductive organs is caused by excessive dietary intake of iron, dysregulation of iron transporters, chronic blood transfusions, and hemochromatosis. Iron overload produces oxidative stress and causes atrophy of ovaries and testes and hypogonadism, which leads to infertility in men and women. Emerging evidence from preclinical and clinical studies suggests that excessive iron-induced infertility results from dysfunction of the hypothalamic-pituitary-gonadal axis and consequently perturbs the secretion of reproductive hormones (GnRH, FSH, LH, estrogen, progesterone, and testosterone). The focus of this review is to summarize the pathophysiology of iron-overload toxicity of sex organs and the reversal of male/female infertility and libido with Ashwagandha. The bioactive ingredients of Ashwagandha appear to restore iron–overload infertility by acting on iron chelation and capturing iron free radicals (Fe+++) produced by the Fenton reaction. Many synthetic drugs have been tried for treating iron overload infertility, but the outcome has been inconsistent. Considering the high cost of these drugs, Ashwagandha may be a safer and more cost-effective phytomedicine to cure iron-overload infertility and enhance libido in humans. Collectively, the iron chelation and antioxidant effects of Ashwagandha seem to reverse iron-overload infertility in men and women by improving testicular and ovarian functions.

Emoxypine and its succinate derivative share a common hydroxypridine structure, which is similar to pyridoxine. These compounds have been utilized therapeutically and industrially, owing to the wide range of properties offered. This includes antihypoxic, neuroprotective and cardioprotective effects, along with pharmacokinetic benefits such as the ability to cross the blood brain barrier (BBB), owing to its relatively small size and low molecular weight. It was observed that emoxypine exhibited iron chelating property in vitro, indicating its usage as a promising therapeutic strategy in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders like thalassemia and hemochromatosis. In addition to this, it has been observed to exert a potent antioxidant effect, therefore, it may be considered for the amelioration of disorders resulting from free radical injury. Studies on its mechanism of action and implications on cellular and molecular levels would help to further the understanding of its benefits, as well as prospects for filing patents for novel applications. The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents.

Curdlan is an exopolysaccharide, which is composed of glucose linked with β-(1,3)-glycosidic bond and is produced by bacteria, such as Alcaligenes spp., Agrobacterium spp., Paenibacillus spp., Rhizobium spp., Saccharomyces cerevisiae, Candida spp., and fungal sources like Aureobasidium pullulan, Poria cocos, etc. Curdlan has been utilized in the food and pharmaceutical industries for its prebiotic, viscosifying, and water-holding properties for decades. Recently, the usefulness of curdlan has been further explored by the pharmaceutical industry for its potential therapeutic applications. Curdlan has exhibited immunoregulatory and antitumor activity in preclinical settings. It was observed that curdlan can prevent the proliferation of malarial merozoites in vivo; therefore, it may be considered as a promising therapy for the treatment of end-stage malaria. In addition, curdlan has demonstrated potent antiviral effects against human immunodeficiency virus (HIV) and Aedes aegypti virus. It has been suggested that the virucidal properties of curdlans should be extended further for other deadly viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19). The prebiotic property of curdlan would confer beneficial effects on the host by promoting the growth of healthy microbiota in the gut and consequently help to reduce gastrointestinal disorders. Therefore, curdlan can be employed in the manufacture of prebiotics for the management of various gastrointestinal dysbiosis problems. Studies on the mechanism of action of curdlan-induced suppression in microbial and tumor cells at the cellular and molecular levels would not only enhance our understanding regarding the therapeutic effectiveness of curdlan but also help in the discovery of new drugs and dietary supplements. The primary focus of this review is to highlight the therapeutic interventions of curdlan as an anticancer, anti-malaria, antiviral, and antibacterial agent in humans. In addition, our review provides the latest information about the chemistry and biosynthesis of curdlan and its applications for making novel dairy products, functional foods, and nutraceuticals and also details about the recent patents of curdlan and its derivatives.

Obesity is a major risk factor involved in the progression of cardiovascular diseases. The aggravation of cardiovascular diseases is primarily linked to the release of pro-inflammatory cytokines. The endocannabinoid system (ECS) plays an important role in various diseases such as obesity, inflammation, Type II diabetes mellitus (T2DM) and cardiovascular dysfunction (CVD). ECS comprises of endocannabinoid receptors; cannabinoid 1 (CB1), cannabinoid 2 (CB2) and cannabinoid enzymes which are responsible for regulation of signaling pathways involved in obesity and CVD. The potential therapeutic interventions by drugs acting on cannabinoid receptors and their usage in the mitigation of obesity and CVD has been demonstrated in various pre-clinical and clinical studies. The expression of CB1 inhibition and CB2 activation receptors has been observed in the CVDs and obesity. Several reports suggest that; inhibition of centrally acting CB1 receptor antagonist show a significant reduction of obesity, atherosclerosis and modulate blood pressure. These therapeutic agents have also been reported to be associated with unwanted side effects. Rimonabant (SR141716/Acomplia/Zimulti), a selective CB1 inverse agonist had shown promising anti-obesity and anti-CVD effects, but later was withdrawn due to severe neuropsychiatric side-effects. The researchers are now exploring alternative approaches to block CB1 receptors by avoiding psychotropic effects. Drugs like TXX-522 have been developed to exhibit good binding capacity to CB1 receptors and have lesser brain penetration. Numerous studies have reported that, CB2 receptor agonists prevent the onset of cardio metabolic diseases by scavenging free radicals and attenuating inflammation. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes inhibition lead to reduction in the reactive oxygen species and regulation of apoptotic pathway, thus ameliorating the elevated biomarkers responsible for obesity and CVD. The central idea of this review is to examine the mechanism of action of cannabinoid receptors and to explore the therapeutic interventions at cellular and molecular levels with respect to their anti-obesity and cardiovascular effects.

Obesity is found to be a contributing risk factor for Cardiovascular Dysfunction (CVD), coronary heart disease (CHD) and heart failure (HF). Obesity is found to be linked to the release of several proinflammatory mediators. The fluctuation in the levels of these mediators and adipocytokines released by the adipocytes further leads to cardiovascular complications. The increase in the risk of CVD and mortality caused by obesity is due to increasing levels of atherosclerotic plaques in the arteries and blood vessels leading to the heart. The current available treatment strategies leads to several unwanted side effects for the patient which leads to a decreased quality of life. Flavonoids are polyphenolic compounds which occur naturally in nature. Several clinical and preclinical studies have demonstrated that flavonoids are beneficial in decreasing the cardiovascular risks presented by obesity. The mechanism of action primarily depends on the antioxidant and anti-inflammatory actions of flavonoids. In view of these observations, the intake of foods containing flavonoids have enormous potential in preventing obesity induced cardio-metabolic diseases. However, randomized and placebo-controlled clinical trials are needed to determine the long-term safety and efficacy of different flavonoids. The focus of this chapter is to highlight the cost-effective health benefits of flavonoid-rich-foods and dietary supplements containing flavonoids for the prevention and cure of obesity linked cardiovascular diseases (CVDs).

Flavonoids consist of a large family of polyphenolic molecules like flavones, flavonols, flavanols, isoflavones, flavanones, and anthocyanidins which are ubiquitously distributed in nature and are present in a wide array of plant products, including fruits, vegetables, and green tea. Because of their powerful antioxidant, anti-inflammatory, and anticancer properties, rigorous research is going on with a number of flavonoids (quercetin, quercitrin, rutin, morin, kaempferol, etc.) to investigate their disease-preventive and health-promoting benefits in humans. Several studies have shown that the cancer prevention and pharmacotherapeutic potential of different flavonoids depend on the type of flavonoid and its chemical structure, bioavailability, effective blood levels, and pharmacokinetic and pharmacodynamic characteristics. Many in vivo and in vitro studies conducted with different types of flavonoids have revealed diverse effects against different types of cancers. However, the major flavonoids (apigenin, luteolin, kaempferol) found in vegetarian diet have depicted limited possibility of curing cancer. In vitro studies done with apigenin and luteolin have shown effectiveness against cervical cancer cells, while kaempferol produced oncolytic effects against gastric and ovarian cancer cells. These flavonoids and their metabolites have revealed different anticancer effects due to their rapid metabolism in the small intestine and liver. Cancers comprise a group of noncommunicable diseases characterized by long-term debilitating illnesses that cause heavy burden on the healthcare system. At present, certain types of cancers are incurable, and palliative interventions are directed to delay the spread of malignant cancer and to ameliorate the painful episodes associated with cancer. The purpose of this review is to focus on the absorption, distribution, metabolism, and excretion (ADME) of different flavonoids and to evaluate the immune-boosting, cancer-preventive, and therapeutic potential of flavonoids against different types of cancers.