Current Bioactive Compounds - Volume 18, Issue 2, 2022

Background: An enhanced knowledge of the multiple effects of ascorbic acid (AA) in health can broaden our understanding of the impacts of its deficiency. Methods: Mice (10-12 month old) were either fed standard rodent feed or AA-fortified diet at 100, 200 and 300 mg/kg of feed, respectively for 8 weeks. On completion of the study, animals were sacrificed, following which haematological, inflammatory/apoptotic marker, oxidative stress markers, and markers of hepatic/renal integrity were assessed. Results: Across the groups, AA fortified diet was associated with an increase in food consumption; however, body weight reduction occurred at the lowest concentration, while weight gain was observed at the higher concentrations. Haematological indices (white cell count, granulocytes, lymphocytes, and red cell count) increased at the highest concentration; while some other red cell parameters decreased. A concentration-dependent improvement in antioxidant status, with the greatest benefit at the highest concentration, was observed. Also, a concentration-dependent modulation of inflammatory markers, lipid peroxidation, lipid profile, and biochemical markers of liver and kidney function was observed. Conclusion: Dietary fortification with AA in middle-aged mice impacted several measurable parameters in a concentration dependent manner. In addition to its antioxidant effects, it was also associated with anti-inflammatory and anti-apoptotic effects.

Background: New 6-hydroxy-5-(p-hydroxybenzylidene)-3-phenyl-2- [(5-pchlorophenyl)- 1,3-thiazol-2-yl]-1, 2, 4-triazine derivatives containing a thiazole ring were synthesised as potential antitumor agents. Methods: Cytotoxicity of compounds (3) and (4) was evaluated in human hepatocellular carcinoma (HCC) cell lines (HepG2); compound (3) showed more cytotoxicity (IC50=9.0μg/ml) than compound (4) (IC50=18.40μg/ml) using doxorubicin as standard. The degree of toxicity of compound (3) was assessed by the LD50 with its anticancer performance by suppressing tumor angiogenesis against diethylnitrosamine (DENA) induced hepatocellular carcinoma (HCC) in male rat model. Results: Carcinogenic rats showed a significant increase in markers of angiogenesis, tumour growth, and liver function tests and malondialdehyde level coupled with reduced hepatic glutathione level and caspase-3 activity. The distribution of compound (3) to animals after the development of HCC improved biochemical alterations from a DENA chemical carcinogen that is confirmed by hepatic histopathology. Conclusion: Compound 3 perhaps utilized as a strong applicant for newly therapeutic protocols against hepatocarcinogenesis by controlling tumor angiogenesis and renovating the activity of hepatic marker enzymes in addition to reversing the oxidant-antioxidant imbalance in corporation with amelioration of histopathology. While the trial supports the use of compound 3 for improved HCC outcome and the toxicity and side effects should be considered.

Background: The fruits, leaves and roots of Morinda species are used in the treatment of inflammations, cancers, diabetes, psychiatric disorders, bacterial and viral infections. However, no study has been conducted on chemical profiling, anti-inflammatory, antioxidant and antimicrobial potentials of leaves of seven Indian Morinda species. Aim: The study aimed to investigate the anti-inflammatory, antioxidant and antimicrobial effects of methanol extract of seven Indian Morinda species. Materials and Methods: The total contents of iridoids, flavonoids, anthraquinone glycosides, triterpenoids, lignans and coumarins from methanol extract of each species were determined by using different established protocols. The anti-inflammatory activity of methanol extracts of each species was evaluated using carrageenan and CFA-induced arthritis in male Wistar albino rats. In vivo, antioxidant activity was determined by estimating the levels of superoxide dismutase, catalase, glutathione and malondialdehyde in liver and kidney homogenates of male Wistar rats. The antimicrobial activity of methanol extracts of all seven species was determined by using the microdilution method against selected microbes. Results: Different values of total contents of iridoids, flavonoids, anthraquinone glycosides, triterpenoids, lignans, and coumarins were achieved from methanol extract of leaf of M. umbellata, M. jasminoides, M. reticulata, M. parvifolia and M. persicaefolia. The potent anti-inflammatory effect was demonstrated (carrageenan-induced paw oedema model) by methanol extract of leaves of M. umbellata at 50 mg/kg dose. Similarly, M. umbellata methanol extract showed maximum antiarthritic effect against CFA-induced arthritis on the 17th day (p.o.). Maximum SOD levels in liver and kidney homogenates were increased by the methanol extract of M. persicaefolia. The catalase concentration was enhanced by the methanol extract of M. jasminoides. GSH level was raised by the methanol extract of leaves of M. umbellata, but M. royoc reduced the levels of MDA in treated animals. The methanol extract of M. parvifolia leaves displayed maximum antibacterial activity against K. pneumoniae. M. persicaefolia methanol extract showed the strongest antifungal activity against P. chrysogenum. Conclusion: The methanol extract of leaves of M. jasminoides, M. reticulata, M. parvifolia, M. umbellata and M. persicaefoli showed promising anti-inflammatory, antioxidant and antimicrobial effects on the studied experimental models.

Introduction: Progress in the development of triazolyl-oxadiazoles, a bisphosphonate- 700 inhibitor, is still continuing with an outcome of the good scaffold as oxadiazole as well as triazoles individually for antibacterial activity. Hence, we have proposed a suitable approach for the synthesis of dual heterocyclic analogues consisting of the therapeutically used non-steroidal anti- inflammatory drugs in a combined form and evaluated their antibacterial and antifungal activities, and conducted docking studies. Methods: The chemical structures were confirmed by various spectroscopic methods like IR, 1H NMR, 13C NMR, mass, and elemental analysis. The antibacterial and antifungal activities of these compounds were screened against Gram-positive and Gram-negative bacteria, and fungal stains, by the agar well diffusion method. The crystal structure of S. aureus complexed with the active site of bisphosphonate BPH-700 (2ZCS) was obtained from the Protein Database (PDB, http://www.rcsb.org). Molecular properties, drug-likeness score, lipophilicity and solubility parameters were assessed by the Molinspiration and Molsoft software 7f (2-NO2, 5-Ome), 7g (3-Cl, 4-Cl), 7a (2-NO2). Results: The synthesised NSAID-triazolyl-oxadiazoles containing 2-nitro-5-methoxy (7f), 3,4- dichloro (7g) derivatives were found to be highly active antibacterial agents against S. aureus and E. coli with MIC values of 16 and 19 μg/mL, respectively. 2-nitro-5-methoxy (7f), 4-bromo (7h) and 2-nitro (7a) derivatives displayed superior antifungal activity against A. niger with MIC values of 56, 76, and 130 μg/mL, respectively. From molecular docking, NSAID linked to 3,4-dichloro analogue (7g) revealed stronger binding interaction (ΔG =7.90 Kcal/Mol) with amino acids Asp49 (1.19 A°), Arg45 (2.17 A°), Lys17, and Lys46 in the active site of S. aureus complexed with bisphosphonate Bph-700 (2ZCS). The compounds following the Lipinski ‘Rule of five’ were synthesized for antimicrobial screening as oral bioavailable drugs/leads. Maximum drug-likeness model score 0.49 and 0.41 was found for compounds 7h and 7b. Discussion: An efficient combination of molecular modeling and biological activity provided an insight into QSAR guidelines that could aid in the further development of these derivatives. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms. The compounds showed suitable drug-like properties and are expected to present good bioavailability pro150;¡le.

Background: Background: Lycium europaeum L. is a medicinal and edible Mediterranean halophyte spiny shrub, however, studies regarding its biological properties focused mainly on its aerial organs. Objective: The objective of the present work was to make a comparative evaluation of the in vitro antioxidant and enzyme inhibitory activities of ethanol extracts and fractions (chloroform, ethyl acetate, n-butanol and aqueous) from roots and leaves of L. europaeum, along with its total phenolic, flavonoid and tannin contents. Methods: The antioxidant activity was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), superoxide radical, β-carotene bleaching, cupric reducing and ferric reducing activity methods. Results: The n-butanol fraction from roots had the highest antioxidant activity in all the assays, and was also the most active against acetylcholinesterase, butyrylcholinesterase and urease (IC50 values of 92.63, 118.26 and 135.60 μgmL-1, respectively). This fraction showed a high level of total phenolic, flavonoid and tannin contents. Conclusion: The results suggest L. europaeum, especially its roots, as a candidate to be further explored as a source of bioactive products.

Background: Considering that many foreign tourists visit Okinawa, Japan, to purchase cosmetic products, there is an urgent need to create cosmetic products native to Okinawa. As the Ryukyu pine tree, which is endemic to Okinawa, has been used as a source of wood, investigating the possible use of its bark is recommended. Using this natural resource from Okinawa would aid in promoting the products of Okinawa’s unique brands. As a result, this study was designed to isolate useful materials for cosmetic production. Therefore, fractionation was conducted based on a few types of chromatographies, after which the extracted product of the Ryukyu pine tree (Pinus luchuensis Mayr.) bark was analyzed, and its polyphenol contents were compared. Methods: Bark of the Ryukyu pine tree cultivated in the northern mountainous region of the Okinawa Main Island was used for ASE extraction using ultrapure water at 130°C. DIAION HP20 with methanol and two HPLC fractionation types were subsequently used for phenolic compound isolation. Results: ASE extraction and HP20 and HPLC fractionations resulted in an isolation of several compounds: threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (compound 1; 0.03% w/w of an ASE extract), erythro-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (compound 2; 0.03% w/w of an ASE extract), catechin (0.11% w/w of an ASE extract), and vanillin (0.31% w/w of an ASE extract). In addition, the value of its antioxidant activity determined by the DPPH (2,2- diphenyl-1-picrylhydrazyl) radical-scavenging capacity assay was 3.3 mmol-trolox eq./g, 2.6 mmol-trolox eq./g, 9.7 mmol-trolox eq./g and 0.7 mmol-trolox eq./g for compound 1, compound 2, catechin, and vanillic acid, respectively. Conclusion: These phenolic compounds possess whitening and anti-aging potentials. Therefore, the Ryukyu pine tree bark would be a useful raw material source for cosmetic production.

Background: The treatment of diabetes involves insulin and many different oral hypoglycemic drugs. In chronic disease conditions, medications potentially lose viability. Therefore, searching for more effective and safer natural anti-diabetic agents has continued to be an important area of investigation. Objective: The present study aims to investigate the effect of ethanolic and aqueous extracts of Schleichera oleosa (S. oleosa) on diabetic rats and isolate and characterize the active compound from an effective extract. Methods:The ethanolic and aqueous extracts were administered orally (200 and 400 mg/kg, for 28 days) to streptozotocin-nicotinamide-induced diabetic rats. Hypoglycemic effects, OGTT, alteration in body weight, lipid profile, biochemical parameters, hepatic enzymes, and histopathological examination were assessed. Afterwards, the active constituents of the effective extract were isolated using column chromatography, and the preliminary structural features were investigated by FTIR, 1H NMR, 13C NMR, and LC/MS. Results: The extracts treated rats showed a significant reduction in the fasting blood glucose level (FBGL), total cholesterol, triglycerides, LDL, VLDL, and stress markers (MDA, SGOT, SGPT), and a significant increase was observed in the concentrations of HDL and bodyweight when compared to the diabetic rat. Furthermore, the extract restored the altered level of antioxidant enzymes and glucose metabolizing hepatic key enzymes. Histopathological evaluation of the pancreas revealed the regeneration of the β-cells in diabetic rats, which was earlier necrosed by streptozotocin. In this study, an active constituent SMK/SO/01 was isolated from the effective ethanolic extract, and further spectral studies confirmed it as belonging to the polyphenolic category. Conclusion: These findings provide scientific evidence that SMK/SO/01 has the potential to be a potential drug candidate for diabetes mellitus and complications induced by the disease. Also, these results prove that ethanolic extract of S. oleosa leaves exerts effective anti-diabetic activity, which provides scientific backing for folklore medicine.