Current Bioactive Compounds - Volume 19, Issue 5, 2023

Aim: The aim of the study was to characterize and investigate the mechanism of action of anti-hyperglycemic and anti-hyperlipidemic constitutents of Allophylus africanus. Background: Allophylus africanus P. Beauv is a medicinal plant commonly used in sub-Sahara Africa for the treatment of metabolic disorders and infectious diseases. Objective: The objective of the study was to isolate and characterize anti-hyperglycemic and antihyperlipidemic chemical constituents from Allophylus africanus, and to investigate the mechanism of their enzymatic inhibitions. Methods: The chemical constituents were isolated using various column chromatographic techniques. The anti-hyperlipidemic and anti-hyperglycemic properties of the chemical constituents were investigated by measuring their inhibitory effects on porcine pancreatic lipase and α- glucosidase enzymes. Fluorescence quenching constants obtained from Stern−Volmer plots were used to determine the mechanisms of inhibitory action. Results: Twelve compounds, of which three were new peptide alkaloids, ethylamino asperphenamate (10), allophylane (11) and allophyline (12), were isolated. The new peptide alkaloids and asperphenamate (9) inhibited porcine pancreatic lipase in a dose-dependent manner with IC50 < 90 μM. Also, 9, 12, stigmasta-5, 22-dien-3-O-β-D-glucoside (3) and eudesmenol (5) inhibited α- glucosidase enzymes with IC50 < 165 μM, which was lower than that of standard drug, acarbose (432.16 ± 6.52 μM). From the Stern-Volmer plots, 9 and 10 indicated a static quenching, while 11 and 12 suggested the occurrence of both static and dynamic quenching mechanisms on porcine pancreatic lipase. On α-glucosidase, only 12 exhibited a concurrent static and dynamic quenching mechanism. Conclusion: The anti-diabesity compounds obtained from A. africanus established its potential for the treatment of metabolic disorders. Among the isolated compounds, three have been reported for the first time in nature while others have been reported for the first time in the plant.

Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.

Background: A member of the Malvaceae family, Azadirachta indica (Neem) is wellknown for its secondary metabolites, including limonoids, flavonoids, triterpenoids, and tetraterpenoids. These compounds have been studied for decades for their bioactivities, including antihemorrhagic and antiproteolytic, which provide information about the use of triterpenoids. Methods: Gedunin was purified by chromatography after being extracted using the Soxhlet method to ensure that it was present in the fruit of the (neem) A. indica plant. ICM Molsoft was used to test the substance for a potential inhibitory effect on the enzymes found in all species of snake venom, including 5'-nucleotidase, acetylcholinetrace, L-aao, metalloproteinase, Results: Our goal is to forecast the pharmacological characteristics of gedunin, which has demonstrated a wide range of activities as a possible antidote for treating patients with snake bites. Our research also shows gedunin has some anti-cancer action in experiments using the cell line HepG2. Conclusion: Gedunin has potential as a medication.

Lung cancer is often associated with the second leading cause of mortality in males globally. Despite clinical advancements, their incidence in humans has not decreased. Hence identifying and developing alternative or complementary therapeutic agents with evidence targeting lung cancer is of considerable interest. Ursolic Acid (UA): a dietary flavonoid present in herbs, vegetables, and fruits can effectively alleviate the hallmarks of lung cancer. As a molecular therapeutic agent, UA disrupts prolonged inflammation, augments antioxidant enzyme defense, attenuates tumor growth signal and tissue invasion/metastasis, limits unrestrained proliferation, fosters apoptosis and regulates immune response in lung cancer. This review will most notably focus on the current source of UA availability, phytochemistry, bioavailability, safety, toxicity, and salient pharmacotherapeutic properties in addition to the preclinical and clinical information currently available to recommend UA as a potential therapeutic agent for lung cancer targeting and prevention.

One of the critical issues that humans worldwide are facing is bacterial infections. Antibiotics were developed as bactericidal agents to avoid the negative consequences of bacterial infections, and they were initially highly efficient against bacteria. However, we face a phenomenon called antibiotic resistance by misusing these chemical antibiotics in this era. In other words, bacteria began to acquire resistance to common antibiotics, and resistance means going back to a time before antibiotics. As it is a significant threat to human health and causes increased mortality, there is a rising demand for novel alternative therapies. An alternate method is to use bacteriophages (phages) as a therapeutic agent against bacterial infections in medicine and agriculture. Phages are viruses capable of infecting pathogenic bacteria, which can cause serious diseases. They do not affect the human microbiota; most only infect certain bacteria. Some research has been done on using phages as a treatment, and more experiments today. For instance, eye infections caused by methicillin-resistant Staphylococcus aureus (MRSA) can be treated by eye drops containing appropriate phages. In this regard, significant progress has been made in phage therapy. This review will discuss the current state of phage therapy, clinical breakthroughs, its superiorities and drawbacks, and the future perspectives of phage applications.

Background: Hepatoprotectors, currently used in clinical practice, often show low efficacy. One of the promising goals in the therapy of liver diseases is the targeted synthesis of smallmolecule drugs with hepatoprotective activity. Some heterocycles, such as 1,4-dihydropyridines, are proven to be good hepatoprotectors. Objective: This study aimed to prepare and investigate the hepatoprotective effects of some dihydro- and tetrahydro pyridines using the experimental rat model of tetrachloromethane (CCl4)- induced acute liver damage. Methods: Several 1,4-dihydropyridines and 1,2,3,4-tetrahydropyridines were synthesized by the reaction of cyanothioacetamide with carbonyl compounds and active methylene compounds, such as Meldrum’s acid, ethyl cyanoacetate or β-keto esters, followed by S-alkylation of intermediate pyridine-2-thiolates. In silico prediction studies were performed to explore the possible protein targets. Using virtual bioscreening tools, we selected the six most promising compounds from the library of new partially saturated pyridines. Six novel compounds were characterized by IR, ¹H, ¹³C DEPTQ NMR spectroscopy, 2D NMR experiments (¹H–¹³C HSQC, ¹H–¹³C HMBC), HRMS (ESI), and elemental analysis. The hepatoprotective effects were studied in vivo on eighty white rats with CCl4-induced liver damage. Biochemical studies, including thymol turbidity test and measurements of levels of bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in the blood of rats, were performed. Results: Five of six studied compounds showed a good hepatoprotective effect on a rat model of tetrachloromethane (CCl4)-induced acute hepatitis. The blood of rats in the experimental groups revealed significantly lower levels of total bilirubin, alanine aminotransferases, aspartate aminotransferases, thymol turbidity and alkaline phosphatase compared to the control group of rats with acute toxic tetrachloromethane hepatitis. Conclusion: Our results suggests that compound, (benzyl 4-(4-chlorophenyl)-5-cyano-6-({2-[(3,4- dimethylphenyl)amino]-2-oxoethyl}thio)-2-methyl-1,4-dihydropyridine-3-carboxylate), can be considered as candidate for further preclinical studies. Moreover, as per our knowledge, this is the first report on the hepatoprotective effects of the 1,2,3,4-tetrahydropyridine series.

The limiting restrictions for any chemical to pass through cellular membranes and be absorbed systematically after oral or topical administration are the molecular size and lipid solubility. Herbal materials are used to make Phytosomes, a new drug delivery method that is easy to make and has a high absorption profile. The pharmacological profile of the drug is also excellent. Due to low lipid solubility and insufficient molecular size, many plant extracts are unable to attain the needed therapeutic value. To penetrate lipid membranes and shield them from germs and digestive enzymes, phytosomes are made utilising phospholipids, predominantly phosphatidylcholine, which has improved bioavailability. A comprehensive literature search of PUBMED, ScienceDirect, SCOPUS and MEDLINE databases yielded the following results: the production procedure, commercial formulations, and medicinal uses are all documented. Phytosomal preparation and drug release behaviour, as well as their applications, are discussed in this review. We have included new information on phytosomal research advancements. The phyto-phospholipid complexes also came up for discussion. To administer powerful and/or unstable medications, the phytosomal drug delivery method may be extremely successful due to the enhanced bioavailability and ease of absorption. According to the findings of this study, the researchers are encouraged to transmit their expertise from labs to the marketplace to further improve these items.