Current Bioactive Compounds - Volume 19, Issue 10, 2023

Background: Tuberculosis (TB) has long been the major infectious cause of mortality, ranking higher than HIV/AIDS as the most common cause of death from a single infectious agent worldwide. The EchA6 target of mycobacteria plays a vital role in synthesizing an important component of the mycobacterial outer membrane. The failure of TB treatment has prompted the investigation of novel anti-tubercular drugs. Objective: This study was aimed at blockage of Mycobacterium tuberculosis cell-wall synthesis via EchA6 inhibition to overcome resistance strain. Methods: Over 3,000,000 compounds and GSK951A (positive control) were investigated as the inhibitors in this study. The GROMACS molecular dynamic package was used to analyze the protein- inhibitor complex's conformational changes under constant temperature and pressure. Also, umbrella sampling (US) was used for free binding energy (ΔG) calculation. Results: Four compounds were chosen for the docking investigation. According to the MD analysis, the studied inhibitors demonstrated good stability and flexibility. According to ΔG obtained from US, the ΔG of GSK951A, ZINC11815220, ZINC67770050, ZINC55048326, and ZINC89700914 were -6.14 kcal mol^-1, -5.25 kcal mol^-1, -10.19 kcal mol^-1, -8.55 kcal mol^-1, and -8.37 kcal mol^-1, respectively. Conclusion: In conclusion, ZINC67770050 is recommended for further study in the laboratory. This investigation is an important starting point for discovering anti-tubercular drugs using EchA6 inhibition.

Aims: This study aimed at developing bioactive peptides by optimization of the enzymatic hydrolysis process of protein from tilapia fish skin waste (Oreochromis niloticus, Linnaeus 1758) using alcalase 2.4.L. Background: Natural bioactive peptides are considered to have low toxicity and therapeutic properties as antioxidants. Objective: The conditions of protein hydrolysis obtained from tilapia fish skin waste (Oreochromis niloticus, Linnaeus 1758) were optimized using alcalase 2.4.l. Methods: In this study, the hydrolysis of protein obtained from tilapia fish skin waste (TFSW) was optimized using alcalase 2.4.L by central composite design (CCD). Degree of hydrolysis (DH), radical scavenging activities (DPPH), and ferric-reducing antioxidant power (FRAP) were used as dependent variables, whereas temperature, pH, and proportion of enzyme to the substrate (PE%) as independent variables. Results: The optimum degree of hydrolysis DH%, DPPH, and FRAP were achieved at a temperature of 58.4132;ƒ, a pH of 8.7, except for DPPH, which was achieved at a pH of 7.0. Conclusion: The present work demonstrated that TFSW could be used as a source to produce bioactive peptides with significant antioxidant activities under specific conditions of enzymatic hydrolysis.

Introduction: Cardiovascular disorders are the most prevalent and life-threatening conditions affecting human beings. Therefore, this study aimed to assess the cardioprotective effect of P. rubra leaves. Aim: Plumeria rubra L. has been used for ages in alternative/traditional systems of medicine for several conditions, such as arthritis, toothache, pruritus, asthma, dysuria, gonorrhoea, diabetes, and various types of inflammation. Methods: Acute toxicity studies were performed using OECD 423 guidelines, and cardiomyopathy was induced in Wistar albino rats through an intraperitoneal injection of doxorubicin hydrochloride. Different groups were established to study the efficacy of doxorubicin-treated P. rubra leaf extract for 7 days. Blood pressure of both systolic and diastolic was recorded with noninvasive blood pressure apparatus, and the mean was considered. Biochemical parameters were analysed for serum and tissue homogenate viz. lactate dehydrogenase (LDH), thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Results: The LD50 cut-off range for the leaf extract was found to be 2,000 mg/kg body weight. P. rubra leaf extract prevented the increase in heart rate (364.8 BPM) and mean blood pressure (122.24 mmHg) and demonstrated good results as an antihypertensive agent. The treatment with the extract was also found to revert the oxidative stress levels, as depicted by the MDA, SOD, and catalase levels in heart tissue in treated rats. Conclusion: P. rubra leaf extract at a higher dose (200 mg/kg) exerted a compelling cardioprotective action against cardiomyopathy induced by doxorubicin in Wistar rats due to the presence of lignan glycoside, liriodendrin.

Background: In addition to being one of the deadliest tumors, breast cancer is also one of the most difficult to cure. Due to the serious side effects of current breast cancer treatments and the rise in drug resistance, current drugs are losing their effectiveness. Potential Natural Bioactives: Bioactive natural compounds target various pathophysiological pathways involved in the development and progression of cancer and hence have the ability to prevent both the growth of breast cancer and the advancement of metastatic disease concurrently. Natural anticancer compounds have been shown to be effective, complementary treatment may be of great assistance in this case. Clinical Outcomes: Nutraceuticals and popular folk remedies may provide benefits over manufactured pharmaceuticals since they have fewer side effects and less toxicity in both in vitro and in vivo studies. A variety of natural compounds have been shown to reduce the aggressiveness of breast cancer, inhibit the growth of malignant cells, and alter the pathways involved in cancer development and progression. Either by directly affecting certain biological targets, such genes, or by indirectly stabilising conjugates that have an impact on metabolic processes, natural compounds called phytochemicals can enhance human health. Mechanistic Pathways: There are many promising bioactive natural products that can be used to treat breast cancer, including those that inhibit aromatase activity, target HIF-1 signaling, inhibit cytoplasmic signaling, modulate epigenetic regulation, modulate estrogen signaling pathways, or work in chemosensitivity/adjuvant therapy (such as resveratrol, epigallocatechin-3-gallate, and eugenol).

Background: Sorghum, a wonder millet, is well known for its beneficial phytochemical profiles. In comparative terms, juice from sweet sorghum has better commercial potential as syrup in several food-based applications. Various sweet sorghum varieties differs in their profile of various phytochemicals, which can impact the commercial potential of sweet sorghum juice. Methods: Our previous works on cultivars developed at ICAR-IIMR were screened for phytochemical, sugar and mineral profile. To give a holistic view of the phytochemical profile of sweet sorghum varieties, the present study is attempted to evaluate the total phenolic and flavonoid content, antihyperglycaemic and cytotoxic profile of the components present in the varieties CSV19SS, SSV84, SSV74. The phytochemical footprint of sweet sorghum juice was studied through HRLCMS. Results: The results showed ethyl acetate extract of SSV84 having potential antihyperglycemic effects with an IC50 of 22.156 ± 0.9 μg/ml (α-glucosidase) and 0.070 ± 0.02 mg/ml (α-amylase) with a comparatively higher phenolic (232.6 ± 1 mg GAE/g) and flavonoid (138.18 ± 0.9 mg QE/g) content. The chloroform extract of SSV 84 showed a higher cytotoxic effect at an IC50 of 165.502 ± 7 μg/ml (HeLa cells) and 237.895 ± 15 μg/ml (Hep G2 cells). HRLCMS profile of SSV 84 showed the presence of long-chain fatty acids in hexane extract. Anthraquinones, carotenoids, xanthophylls, cinnamic acid and derivatives, and isoflavones were present in chloroform extract, while Ethyl acetate extract was rich in phenolic acids and also consisted of coumarins, quinones, alkaloids, and terpenoids. Conclusion: The high cytotoxic and antihyperglycemic activities of extracts can be attributed to the presence of these phytochemicals.

Aim: The primary goal of this study is to create a novel naproxen sodium-loaded ethosome drug delivery system for improving bioavailability, solubility and optimize using a statistical approach. Background: Naproxen sodium (i.e., a non-steroidal anti-inflammatory drug) is chosen as the first line of treatment for rheumatoid arthritis and ankylosing spondylitis. However, naproxen has side effects, such as bronchospasm, an irregular heart rhythm, etc. Therefore, adopting new drug delivery strategies when developing the dosage form is necessary and the need of the hour to prevent its side effects. The available commercial products are administered through the oral and parenteral routes, which lack bioavailability and permeability respectively. Objective: Novel ethosomal carriers were designed using Box Behnken Design (BBD) and formulation was prepared for enhanced topical delivery of naproxen sodium ethosomal gel. Methods: In order to analyze the data statistically and graphically with response surface plots, the Box-Behnken design was used to optimize the formulation variables. The independent factors were phosphatidylcholine (X1), cholesterol (X2), and ethanol (X3), while the dependent variables were entrapment efficiency (Y2), vesicle size (Y1), and PDI (Y3). The Carbopol® 940 gel was then made using the improved ethosomes. Its rheological properties, in-vitro release, ex-vivo skin penetration, and deposition were studied. Results: The best ethosomes were made by mixing phosphatidylcholine and cholesterol in a phosphate buffer at pH 7.4 with 2–5% v/v ethanol. The optimized ethosomes showed a zeta potential of -32.06 ± 0.16 mV, EE of 84.59 ± 2.38%, and a vesicular size of 105 ± 6.97 nm. Compared to the commercial products and the ethanolic solution of naproxen, these ethosomes considerably increased the amount of naproxen permeated through the skin over 24 hours. The stability of the optimized formulation was assessed for three months at room temperature, and it was found that the efficiency of the prepared novel ethosomal formulation remained intact. Conclusion: In summary, it was discovered that the ethosomal vesicles were potential carriers, showing the improved topical distribution of naproxen sodium. These findings demonstrated that using ethosomes as a transdermal medication carrier for naproxen was feasible. Compared to drug solutions, the ex-vivo permeation and skin deposition experiments produced better results.

Psoriasis is a hereditary, immune-mediated illness that can affect the skin, joints, or both. The condition frequently requires the treatment of a wide group of specialists with a variety of specialties. Numerous difficulties are presented by psoriasis, such as its high prevalence, chronicity, disfigurement, disability, and related comorbidities. Natural treatment of psoriasis can be provided by flavonoids and furanocoumarins. Flavonoids, a group of chemical compounds with various phenolic structures, are found in a wide variety of foods, including fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. The health benefits of these natural compounds are well known, and efforts are being made to extract the components known as flavonoids. Furanocoumarin is a subgroup of coumarins with phenolic compounds. It can be divided into two groups: linear generic name psoralens, which include psoralen, xanthotoxin, and bergapten, and angular generic name angelicins, which include sphondin and pimpinellin. The most important plant source is psoralen, which has been used for generations in traditional medicine to treat psoriasis and vitiligo. The creation of alternative psoralen molecules that do not generate the bifunctional adducts that serve as the foundation for DNA crosslinking is one of the future directions for further improving psoriasis treatment. This article focuses on flavonoid and furanocoumarin research and development trends, modes of action, functions, and applications.

Inflammation is a part of the biological response of body tissues against harmful stimuli, such as damaged cells, pathogens, irradiations, and toxic compounds. Numerous treatments, including anti-inflammatory drugs that treat the condition of inflammation, are available for its management. Because of the severe adverse effects associated with synthetic medications, phytotherapy may be a promising and effective approach to treating inflammation. The therapeutic potential of herbs is due to their capacity to target a variety of inflammatory mediators, including chemokines, cytokines, nitric oxide, lipoxygenase, nuclear factor kappa-B, and arachidonic acid. Furthermore, nanomedicine may be a valuable and effective formulation approach for overcoming the drawbacks of phytoconstituents, such as their low bioavailability, high first-pass metabolism, and poor stability. The current manuscript provides a thorough description of many phytoconstituents and herbal plants that have great potential for treating inflammation-related diseases, as well as information on their limitations, drug formulations, and regulatory issues.