In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég).

Background: Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. Aim: The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. Results: Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[ß-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. Conclusion: Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.

Bioactive synergism between zinc mineral and p-coumaric acid: A multi-mode glycemic control and antioxidative study.

Natural supplements are important in diabetes and oxidative stress management. A complexation-mediated antihyperglycemic and antioxidant synergism between zinc(II) and p-coumaric acid was investigated. p-Coumaric acid was complexed with ZnSO4 and characterized by FT-IR, 1 H NMR, and mass spectroscopy. The antioxidant and antihyperglycemic potential of the complex and precursors were evaluated with different experimental models. Molecular docking with target proteins linked to diabetes was performed. A Zn(II)-bicoumarate.2H2 O complex was formed. The in vitro radical scavenging, α-glucosidase inhibitory, antiglycation, and anti-lipid peroxidative activities of the complex were several folds stronger than p-coumaric acid. In Chang liver cells and rat liver tissues, the complex inhibited lipid peroxidation (IC50  = 56.2 and 398 µM) and GSH depletion (IC50  = 33.9 and 38.7 µM), which was significantly stronger (2.3-5.4-folds) than p-coumaric acid and comparable to ascorbic acid. Zn(II) and p-coumaric synergistically modulated (1.7- and 2.8-folds than p-coumaric acid) glucose uptake in L-6 myotubes (EC50  = 10.7 µM) and rat muscle tissue (EC50  = 428 µM), which may be linked to the observed complexation-mediated increase in tissue zinc uptake. Glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Docking scores α-glucosidase, GLUT-4, and PKB/Akt showed stronger interaction with the complex (-6.31 to -6.41 kcal/mol) compared to p-coumaric acid (-7.18 to -7.74 kcal/mol), which was influenced by the Zn(II) and bicoumarate moieties of the complex. In vitro, the complex was not hepatotoxic or myotoxic. Zn(II) complexation may be a therapeutic approach for improving the antioxidative and glycemic control potentials of p-coumaric acid. PRACTICAL APPLICATIONS: In functional medicine, natural supplements, plant-derived phenolics, and nutraceuticals are becoming popular in the management of diseases, including diabetes and oxidative stress. This has been largely attributed to their perceived holistic medicinal profile and the absence of notable toxicity concerns. In the past two decades, considerable attention has been drawn toward zinc mineral as a possible therapeutic supplement for diabetes due to its role in insulin secretion and reported insulin mimetic potentials. p-Coumaric acid is a known natural antioxidant with reported diabetes-related pharmacological effects. In this study, we took advantage of these properties and complexed both natural supplements, which resulted in a more potent nutraceutical with improved glycemic control and antioxidant potential. The complexation-mediated synergistic interaction between zinc and p-coumaric acid could be an important therapeutic approach in improving the use of these natural supplements or nutraceuticals in managing diabetes and associated oxidative complications.

Nutritional and phytochemical profile of pomegranate ("Wonderful variety") peel and its effects on hepatic oxidative stress and metabolic alterations.

The peel of pomegranate fruit contains antioxidant phytochemicals that may potentiate health benefits but remain under-explored. We evaluated the antioxidant, nutritional and phytochemical profiles of the peel of the "Wonderful" variety pomegranate and its influence on oxidative metabolic alterations in hepatic tissue. The peel contained appreciable amounts of some beneficial trace minerals and both essential and non-essential amino acids. Mostly Omega 3 and 6 fatty acids were found. The peel extracts exhibited in vitro radical scavenging and Fe3+ reducing antioxidant activities and dose-dependently prevented oxidative stress-induced lipid peroxidation increase and GSH depletion in both Chang liver cells (IC50 = 18.0 ± 1.46 and 11.2 ± 0.99 µg/mL, respectively) and isolated rat liver (IC50 = 96.7 ± 3.34 and 19.4 ± 3.36 µg/mL, respectively). The antioxidant effects were comparable to that of ascorbic and correlated with their phenolic profile. HPLC analysis further identified antioxidant phenolic acids (gallic acid, syringic acid ferulic acid p-coumaric acid or trans-4-hydroxycinnamic acid, etc.). The peel did not cause notable cytotoxicity in liver and kidney cells, which suggest minimal safety concerns. Metabolomics analysis revealed alterations in fatty acid, amino acids, and nucleic acid metabolisms following the induction of oxidative stress. These alterations were improved in the acetone extract-treated tissues, with concomitant activation of vitamin and selonocompound metabolisms. Data suggest that the fruit peel of "Wonderful" pomegranate may be an underutilized source of functional nutrients and antioxidants phenolic acids for optimum body function and mitigation hepatic oxidative damage and metabolic alterations as well as associated diseases. PRACTICAL APPLICATIONS: Although underutilized, documented evidence have shown that the wastes, like peels from fruits contain more phytochemicals than the edible pulp, making them potential sources of bioactive principles. In this study we exposed the nutritional, phytochemical and oxidative stress-related medicinal benefits of the peel of "Wonderful" pomegranate variety. The peel could ameliorate oxidative hepatic metabolic alterations. The peel of this fruit could be a source of beneficial micro and macro nutrients, as well as bioactive phenolics to improve oxidative health and mitigate oxidative hepatic damage and associated disease states. Medicinally utilizing the fruit's peel could reduce underutilized fruit wastes, increase the value of the fruit and benefit the bioeconomy.

Genotoxic effects of Dukhan: A smoke bath from the wood of Acacia seyal used traditionally by Sudanese women.

ETHNOBOTANICAL RELEVANCE: Smoke from the wood of Acacia seyal Delile has been used by Sudanese women for making a smoke bath locally called Dukhan. The ritual is performed to relieve rheumatic pain, smooth skin, heal wounds and achieve general body relaxation. AIM OF THE STUDY: The present study was designed to investigate the in vitro anti-inflammatory effect of the smoke condensate using cyclooxygenase -1 (COX-1) and -2 (COX-2) as well as its potential genotoxic effects using the bacterial-based Ames test and the mammalian cells-based micronucleus/cytome and comet assays. MATERIAL AND METHODS: The smoke was prepared in a similar way to that commonly used traditionally by Sudanese women then condensed using a funnel. Cyclooxygenase assay was used to evaluate its in vitro anti-inflammatory activity. The neutral red uptake assay was conducted to determine the range of concentrations in the mammalian cells-based assays. The Ames, cytome and comet assays were used to assess its potential adverse (long-term) effects. RESULTS: The smoke condensate did not inhibit the cyclooxygenases at the highest concentration tested. All smoke condensate concentrations tested in the Salmonella/microsome assay induced mutation in both TA98 and TA100 in a dose dependent manner. A significant increase in the frequency of micronucleated cells, nucleoplasmic bridges and nuclear buds was observed in the cytome assay as well as in the % DNA damage in the comet assay. CONCLUSIONS: The findings indicated a dose dependent genotoxic potential of the smoke condensate in the bacterial and human C3A cells and may pose a health risk to women since the smoke bath is frequently practised. The study highlighted the need for further rigorous assessment of the risks associated with the smoke bath practice.

A review on the medicinal potential, toxicology, and phytochemistry of litchi fruit peel and seed.

The perception that many fruit wastes, particularly the peel, contain more phytochemicals than the edible portions has been largely supported by scientific evidence, making them potential sources of bioactive and therapeutic phytochemicals. The peel and seed of Litchi (Litchi chinensis Sonn.) contain bioactive principles and have been shown to exhibit antioxidative, antidiabetic, cancer preventive, anti-obesogenic, and anti-inflammatory properties. This review presents a critical analysis of previous and current perspectives on the medicinal, toxicological, and phytochemical profiles of litchi fruit peel and seed, thus providing an evidence-based platform to explore their medicinal potential. A literature search was done on "PubMed," "Google Scholar," and "ScienceDirect." Peer-reviewed published data on the medicinal profiles of litchi fruit peel and seed were identified and critically analyzed. The fruit peel and seed improved glycemic control and insulin signaling and downregulated lipogenic and cholesterogenic processes. Their neuroprotective, hepatoprotective, and renal protective potentials were influenced by antioxidative and anti-inflammatory actions. The anticancer effect was mediated by upregulated proapoptotic, proinflammatory, antiproliferative, and anti-metastatic processes in cancer cells. Simple flavonols, sesquiterpenes, phenolic acids, jasmonates, and proathocyanidins are the possible bioactive principles influencing the medicinal effects. Appropriate toxicity studies are, however, still lacking. Litchi fruit wastes may be further studied as useful sources of therapeutic agents that may have medicinal relevance in oxidative, metabolic, vascular, and carcinogenic ailments. PRACTICAL APPLICATIONS: Underutilized fruit wastes contribute to environmental pollution. Interestingly, these wastes contain phytochemicals that could be of medicinal relevance if their medicinal potentials are maximized. Litchi fruit is a widely consumed fruit with commercial value. Its peel and seeds contribute to fruit wastes. The review exposes the medicinal potential and bioactive principles and/or nutrients of the fruit's peel and seed while elucidating the underlying therapeutic mechanisms or modes of actions through which litchi peel and seed potentiate medicinal effects. Thus, the review provides an evidence-based platform to explore the medicinal potential of underutilized wastes from litchi fruit. Additionally, the fruit peel and seed could be low-cost residues that could afford ecofriendly opportunity if their medicinal potentials are properly maximized.

Vanillic acid-Zn(II) complex: a novel complex with antihyperglycaemic and anti-oxidative activity.

OBJECTIVES: Our aim was to synthesize, characterize and evaluate the antihyperglycaemic and anti-oxidative properties of a new Zn(II) complex of vanillic acid. METHODS: The complex was synthesized using ZnSO4.7H2O and vanillic acid as precursors. NMR and FTIR techniques were used to characterize the synthesized complex. The cytotoxicity of the complex was measured. The antihyperglycemic and anti-oxidative properties of the complex were evaluated using in vitro, cell-based and ex vivo models and compared with those of its precursors. KEY FINDINGS: Zn(II) coordinated with vanillic acid via a Zn(O6) coordination, with the complex having three moieties of vanillic acid. The radical scavenging, Fe3+ reducing and hepatic antilipid peroxidative activity of the complex were, respectively, 2.3-, 1.8- and 9.7-folds more potent than vanillic acid. Complexation increased the α-glucosidase and glycation inhibitory activity of vanillic acid by 3- and 2.6-folds, respectively. Zn(II) conferred potent L-6 myotube (EC50 = 20.4 µm) and muscle tissue (EC50 = 612 µm) glucose uptake effects on vanillic acid. Cytotoxicity evaluation showed that the complex did not reduce the viability of L-6 myotubes and Chang liver cells. CONCLUSIONS: The data suggest that Zn(II)-vanillic acid complex had improved bioactivity relative to vanillic acid. Thus, Zn(II) may be further studied as an antihyperglycaemic and anti-oxidative adjuvant for bioactive phenolic acids.

Zinc(II) mineral increased the in vitro, cellular and ex vivo antihyperglycemic and antioxidative pharmacological profile of p-hydroxybenzoic acid upon complexation.

In this study, zinc was complexed with p-hydroxybenzoic acid to synthesize a complex with improved pharmacological profile. Proton NMR and FTIR analysis were used to characterize the complex. Several in vitro, cellular and ex vivo antihyperglycemic and antioxidative assays were used to evaluate the potency of the complex, relative to its precursors, while molecular docking was used to investigate interactions with insulin signaling targets (GLUT-4 and PKB). Also, the cytotoxicity of the complex was evaluated in Chang liver cells and L-6 myotubes using MTT assay. Complexation was through a Zn(O4 ) coordination. This afforded the complex two moieties of p-hydroxybenzoic acid, which influenced its activities. While the complex retained the α-glucosidase and α-amylase inhibitory activity of its phenolic acid precursor, complexation increased in vitro and ex vivo antioxidant activity of the phenolic acid by 1.4 to 10.5-folds. Complexation, further, conferred a potent antiglycation activity and L-6 myotube and psoas muscle glucose uptake properties (2.1 to 3.5-folds more than p-hydroxybenzoic acid) on the phenolic acid, without notably inhibiting or reducing the viability of Chang liver cells (IC50  = 5,120 µM) and L-6 myotubes (IC50  = 2,172 µM). Docking studies showed the complex had better interactions with insulin signaling targets (GLUT-4 and PKB) than p-hydrobenzoic acid, which may influence its glucose uptake effects. Data suggest that Zn(II) complexation improved and/or broadened the pharmacological profile of p-hydroxybenzoic acid, thus, may be further studied as a promising adjuvant for phenolic acids. PRACTICAL APPLICATIONS: Most antidiabetic drugs are used as two or more combinations to achieve better efficacy, which may cause drug interaction and increase the risk of side effects associated with these drugs. This study takes advantage of the glycemic control property of zinc and the antioxidant and/or diabetes-related pharmacological properties of p-hydroxybenzoic acid to form a complex with improved and broader antioxidant and antihyperglycemic profile and minimal toxicity concerns. With appropriate further studies, Zn(II)-phenolic acid complexes may be safe nutraceuticals for diabetes and related oxidative complications.

Isolation of anti-mycobacterial compounds from Curtisia dentata (Burm.f.) C.A.Sm (Curtisiaceae).

BACKGROUND: Tuberculosis is counted amongst the most infectious and lethal illnesses worldwide and remains one of the major threats to human health. The aim of the current study was to isolate and characterize anti-mycobacterial compounds present in Curtisia dentata (Burm.f.) C.A.Sm , a medicinal plant reportedly used in the treatment of tuberculosis, stomach ailments and sexually transmitted infections. METHODS: The bioassay guided principle was followed to isolate the anti-mycobacterial compounds. The crude ethanol extracts of the leaves was partitioned with various solvents four compounds such as ß-sitosterol, betulinic acid, ursolic acid and lupeol were successfully isolated. The compounds and their derivatives were evaluated for anti-mycobacterial activity using Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis H37RV (ATCC 27294). Furthermore, the derivatives were investigated for their toxicity against HepG2 and HEK293 using the MTT assay. RESULTS: The methanol fraction had the lowest minimum inhibitory concentration (MIC) of 22.2 µg/ml against the selected Mycobacterium strain when compared to other fractions. Ursolic acid acetate (UAA) was the most active compound with MIC value of 3.4 µg/ml. The derivatives had varying degrees of toxicity, but were generally non-toxic to the selected cell lines. Derivatives also exhibited highest selectivity index and offers a higher safety margin. CONCLUSIONS: The derivatives had better antimicrobial activity and low cytotoxic effects compared to isolated compounds. These increased their selectivity. It appears that acetylation of both betulinic acid and ursolic acid increased their activity against the selected Mycobacterium species. The results obtained in this study gives a clear indication that Curtisia dentata may serve as major source of new alternative medicines that may be used to treat TB. Furthermore, there is a need to explore the activity of these tested plant against other pathogenic Mycobacterium species.

Ochnaflavone and ochnaflavone 7-O-methyl ether two antibacterial biflavonoids from Ochna pretoriensis (Ochnaceae).

The acetone extract of Ochna pretoriensis was evaluated for antibacterial activity using bioautography and serial microplate dilution methods against four nosocomial bacterial pathogens namely: Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. A bioassay-guided fractionation of the crude extract led to the isolation of two antibacterial biflavonoids, ochnaflavone and ochnaflavone 7-O-methyl ether. Gram-negative bacteria were more sensitive to the isolated compounds than the Gram-positive bacteria (MIC values: 31.3 microg/mL for P. aeruginosa and 62.5 microg/mL for S. aureus). In addition, the isolated compounds were assessed for their potential toxic effects in the MTT toxicity assay using monkey kidney vero cells and Ames genotoxicity test using Salmonella typhimurium strain TA98. LC50 values were 125.9 microg/mL for ochnaflavone and 162.0/microg/mL for ochnaflavone 7-O-methyl ether. The isolated compounds have selectivity index values ranging from 1.29 to 4.03. Selectivity index values higher than one indicate that test samples are less toxic to the host cells than to the pathogens. The biflavonoids did not have any mutagenic effects in the Salmonella/microsome assay without metabolic activation.