Current Bioactive Compounds - Volume 19, Issue 7, 2023

Silymarin, a flavonolignan derived from the seeds extract of Silybum marianum (milk thistle), has been frequently used since ancient times. It is made up of flavonolignans such as silychristin, isosilybin A and B, dehydrosilybin, and silybin as well as flavonoids like taxifolin, with silibinin being the most active. Silibinin is a diastereoisomeric combination of two flavonolignans, silybin A and silybin B, with a diastereoisomeric structure. It is found in a variety of phytopreparations that are used to prevent and treat liver disorders. It is considered an important component in a huge range of cosmetic, pharmacological, and medical formulations. Several investigations have revealed that silibinin has anticancer and chemopreventive properties, as well as hypocholesterolaemic, antimicrobial, antidiabetic, anticancer, antihypertension, antiparkinson, antiinflammatory, antioxidant, cardioprotective, and neuroprotective benefits by the help of different mechanisms such as inducing apoptosis, decreasing cell proliferation, inhibiting angiogenesis and viral transition and its entry, and also regulating insulin secretion by decreasing or increasing the expression of sterol regulatory element binding protein-1c (SREBP-1C) and insig-1 transcription factor, etc. Silibinin data is gathered from many public databanks in order to emphasize its important role in the treatment or prevention of various diseases.

Background: Hemorrhoids are anorectal disorders characterized by dilation of rectal blood vessels, inflammation, and prolapse of the anal tissue. The disease affects both men and women equally. In consequence, the increasing prevalence of the disease needs potential agents with efficiency and low cost to support the treatment. Objective: The treatment of hemorrhoids in modern medicine is still found to be in its infancy, as there is no precise treatment for the specific disease. Tridax procumbens Linn (T. procumbens) belongs to the family Asteraceae. From the literature, the plant was found to have a traditional use for the treatment of hemorrhoids. Hence, the present research was focused on evaluating the antiinflammatory mediated anti-hemorrhoidal potential of ethanolic whole plant extract of T. procumbens (EWETP) in croton oil-induced hemorrhoidal rats. Methods: An in vitro study was conducted to evaluate the percentage inhibition of protein (egg albumin) denaturation by Tridax procumbens. This study determined the initial protective role of plant extracts against inflammatory proteins. An in vivo, anti-inflammatory-mediated anti-hemorrhoidal study was carried out on T. procumbens in various groups of croton oil-induced hemorrhoidal rats. Wistar albino rats were selected for the present research, and hemorrhoids were induced in experimental animals using a croton oil preparation containing 6% croton oil, deionised water, pyridine, and diethyl ether. Pilex ointment was taken as a reference drug in this study. Inflammation seems to be a major pathway for the progression of hemorrhoids. Hence, in the present research, Evans blue (EB) extravasation technique was applied to quantify inflammatory proteins. On the last day of the study, blood samples were drawn from experimental animals to analyse serum and blood for TNF- α, IL-6, and the percentage of neutrophils count. Recto anal coefficient was calculated to measure croton oil-induced rectal inflammation in animals. Histopathological studies were carried out separately on a second set of animals to identify the protective role of T.procumbens on rectal tissue cell histology. Molecular docking studies were carried out to rule out the possible interaction of plant phytoconstituents with the COX-2 enzyme. Results: Results showed that intra rectal application of croton oil preparation in albino rats developed hemorrhoids by elevating serum TNF-α and IL-6 in positive control group animals compared to normal group rats. Treatment of albino rats with T. procumbens at doses of 200 mg/kg and 400 mg/kg in groups IV and V has shown a significant reduction in serum TNF-α and IL-6. Furthermore, in the study, T. procumbens exhibited a significant dose-dependent reduction of EB dye extravasation in study animals. The study observations also revealed the inhibitory effect of plant extract on the blood percentage of neutrophils count and recto anal coefficient compared to the positive control group rats. Histopathological studies conducted on rectoanal tissues showed the presence of minimal rectal tissue changes in plant extract-treated group animals compared to positive control group rats. Molecular docking studies explored the possible interaction of phenolic compounds of plant extract with the COX enzyme. Conclusion: It was concluded that Tridax procumbens had a protective role against inflammatory mediators in hemorrhoids. In hemorrhoidal rats, ethanolic leaf extract was found to reduce the plasma percentage of neutrophils and other inflammatory cytokines, TNF-α, and IL-6. It could be used as a therapeutic anti-inflammatory mediated anti-hemorrhoidal agent.

Background: The aim of our study was to investigate the mechanisms of oil-related product toluene and functional food flaxseed Linum usitatissimum L. on ovaries in humans and the potential protective effect of flaxseed against adverse toluene action. We examined 1) the action of toluene (at doses 0, 10, and 100 ng/ml), 2) flaxseed extract (10 μg/ml), and their combination on cultured human ovarian granulosa cells. Methods: Viability, markers of proliferation (accumulation of PCNA) and apoptosis (accumulation of bax), the release of steroid hormones, IGF-I, oxytocin, and prostaglandin F were analyzed by Trypan blue exclusion test, quantitative immunocytochemistry, and EIA/ELISA. Results: Toluene suppressed all analyzed ovarian parameters. Flaxseed stimulated proliferation, progesterone and IGF-I and reduced prostaglandin F output. The presence of flaxseed supported toluene action on cell viability and apoptosis and inverted its effect on proliferation, progesterone, testosterone, and IGF-I release. Conclusion: These observations a) confirm direct inhibitory/toxic action of toluene on ovarian cells, b) demonstrate the ability of flaxseed to affect ovarian cell functions, c) show the ability of flaxseed to prevent some toxic effect of toluene, and d) indicate the that flaxseed could be a biostimulator of human reproduction and protector against the adverse influence of toluene on female reproduction.

Garcinia indica (also known as kokum) is a small evergreen tree that has been used in a variety of culinary, industrial, and pharmacological products, as well as fruit juices and food. In the present study, the antioxidant capacity of anthocyanin extracted from Garcinia indica fruit waste was assessed using DPPH, ABTS assay, and a Caenorhabditis elegans infection model. The independent variables, such as temperature, solvent concentration, microwave exposure, and exposure to ultrasonication were integrated as independent variables in a five-level central composite design using response surface methodology. Based on statistical analysis, the generated models were successfully utilised to analyse the experimental data and determine the best extraction conditions. The rescue effect of anthocyanin was further studied using a paralysis and killing assay in a C. elegans infection model. The extraction yield was 21.0 mg/g under these conditions, with antioxidant activity of 9.9 μg/ml by ABTS assay and 6.6 μg/ml by DPPH assay, respectively. Furthermore, as compared to ethanol leaching extraction, this experimental design increased anthocyanin yield by more than 15 fold. The treatment of anthocyanin with C. elegans from E. coli and Pseudomonas aeruginosa PAO1 infection resulted in a significantly longer lifetime. Garcinia indica fruit waste extracts high in anthocyanins might be employed as natural food colorants and antioxidant additives in food products.

Aims: To investigate the effect of R. hypocrateriformis extract on the production of proinflammatory cytokines by macrophages. Background: The whole plant was extracted with ethanol at room temperature. The in vitro antiinflammatory activity of RH was investigated on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Objective: LPS-induced nitric oxide (NO) production was determined by the Griess method. Production of pro-inflammatory cytokines including Interleukin-1 beta (IL-1 β), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) was examined using reverse transcriptase - polymerase chain reaction (RT-PCR) and Western blot analysis. Under in vitro conditions, RH in doses ranging from 6.25 - 100 μg/mL significantly inhibited lipopolysaccharideinduced nitric oxide production and the production of pro-inflammatory mediators. Methods: In vitro determinations of the toxic effects of unknown compounds have been performed by counting viable cells after staining with a vital dye. Alternative methods used are the measurement of radioisotope incorporation as a measure of DNA synthesis, counting by automated counters, and others that rely on dyes and cellular activity. The MTT system is a means of measuring the activity of living cells via mitochondrial dehydrogenases. The MTT method is simple, accurate, and yields reproducible results. Results: In this study, we investigated whether R. hyocrateriformis can inhibit the production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in LPS-activated macrophages. In addition to its pivotal role in many body functions, NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis. Conclusion: R. hypocrateriformis extract suppressed the pro-inflammatory cytokine production in LPS-stimulated RAW264.7 macrophages. Hence, R. hypocrateriformis extract is a potential candidate for the development of pharmacological agents useful in the treatment of inflammatory diseases. Further research on the effects and molecular mechanisms of the active compound in the extract is needed to precisely define thestructure-activity relationship in various molecular regulatory mechanisms.

Background: Calotropis procera (Aiton) (Apocynaceae) is a traditional Indian medicinal plant and used in folk medicine for the past decade for the treatment of gastrointestinal disorders. Therefore the current investigation was undertaken to explore the gastroprotective effect of C. procera (Aiton) leaves extract using pylorus ligation-induced gastric ulcer in rats. Methods: The crude powder material was successively extracted with different solvents and concentrated at reduced pressure in a rotary evaporator. The current investigation was carried out by a pylorus ligation-induced gastric ulcer model in rats. Omeprazole, 20 mg/kg and 100, 250, and 500 mg/kg ethanol extract of C. procera (Aiton) leaves were administered orally for 15 consecutive days, on the last day six hours after pylorus ligation animals were sacrificed and the amount of gastric juice, pH, total and free acidity, ulcer index, and pro-inflammatory cytokines along with antioxidant parameters and total protein were also studied. Results: Pretreatment of C. procera (Aiton) leaf extract at the doses 250 and 500 mg/kg, significantly (p < 0.001) decrease the volume of gastric juice, free and total acidity as well as gastric lesions, and secretion of pro-inflammatory cytokine. On the other hand, the pH of gastric juice, mucin content, and total protein was also significantly decreased. Moreover, pretreatment of C. procera (Aiton) significantly (p < 0.001) boost the enzymatic activity and level of different antioxidant markers and attenuated the pylorus ligation-induced level of MDA (p < 0.05) in experimental animals. Conclusion: From this study, it is concluded that the ethanol leaf extract of C. procera (Aiton) extract possess considerable antiulcer and antioxidant potential. For further research findings, it is necessary to explore the mechanism of action for anti-ulcer activity.

Background: Disturbances in the sleep cycle have been often associated with the depletion of oxidant enzymes and deposition of beta-amyloid plaques leading to neurodegeneration in Alzheimer's disease (AD). Healthy sleep time and sleep cycles were proven to clear the betaamyloid out of the brain and also promote the synthesis and functions of anti-oxidant enzymes. Objective: Jasmonic acid was evaluated to enhance the cognition and acetylcholine enzyme in the sleep deprivation-induced Alzheimer's by using the zebrafish model. Methods: The molecular properties, bioactivity score, and pharmacokinetic parameters of jasmonic acid were predicted using Molinspiration, SwissADME, and PreADMET tools. Jasmonic acid obeys Lipinski's rule and has significant bioavailability and blood-brain barrier penetration. The prediction of binding energy and interactions of jasmonic acid with six selected receptors was performed using AutoDock 4.2 software. It has significant binding affinity and interactions with different receptors which predict a multi-target potential using in-silico studies. In vivo neurobehavioral analysis of jasmonic acid was performed with zebrafish by using T-maze, Y-maze, and inhibitory avoidance apparatus and the results reveal Jasmonic acid produces more memory retention in zebrafish. In vitro assays of jasmonic acid on acetylcholinesterase enzyme level, glucose level, catalase activity, and lipid peroxidation activity were performed. Jasmonic acid shows cholinesterase inhibition, it acts as a good anti-oxidant and increases glucose metabolism on zebra fish brain homogenate using various assays. Jasmonic acid decreases neurodegeneration, and amyloid deposits in zebrafish brains using histopathological studies. Results: In silico molecular docking studies, in vitro assays, in vivo neurobehavioral analysis and histopathological studies reveal that jasmonic acid showed significant activity against sleep deprivation- induced AD in the zebrafish model. Conclusion: Hence, jasmonic acid will be carried out for further preclinical and clinical studies in order to prove the same for the management of Alzheimer's disease.

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 sex hormones (GnRH, FSH, LH, estrogen, progesterone, and testosterone). The focus of this review is to summarize the pathophysiology of iron-overload toxicity of reproductive 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 costeffective 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.