Antimicrobial and anti-virulence activities of 4-shogaol from grains of paradise against gram-negative bacteria: Integration of experimental and computational methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacterial resistance to antibiotics is a growing global concern, highlighting the urgent need for new antimicrobial candidates. Aframomum melegueta was traditionally used for combating urinary tract and soft tissue infections, which implies its potential as an antimicrobial agent. AIM OF STUDY: This study was designed to explore the antibacterial and anti-virulence capabilities of 4-shogaol isolated from A. melegueta seeds versus gram-negative bacteria: Serratia marcescens, Klebsiella pneumoniae, Acinetobacter baumannii, and the clinically important pathogen Pseudomonas aeruginosa. MATERIALS AND METHODS: 4-Shogeol was isolated from A. melegueta seeds and its MICs were determined for Acinetobacter baumannii (ATCC-17978), Pseudomonas aeruginosa (ATCC-27853), Klebsiella pneumoniae (ATCC-700603), and Serratia marcescens clinical isolate. The anti-efflux activity and effect on the bacterial cell membrane for the compound were evaluated. Furthermore, the anti-virulence activities of the compound were evaluated. The effects of 4-shogeol at sub-MIC on bacterial motility, biofilm formation, and production of virulent enzymes and pigments were assessed. The anti-quorum sensing activities of 4-shogeol were evaluated virtually and by quantification its effect on the expression of quorum sensing encoding genes. The in vivo protection assay was conducted to evaluate the effect of 4-shogaol on the P. aeruginosa capacity to induce pathogenesis in mice. Finally, the effect of shogaol-antibiotics combination was assessed. RESULTS: The research revealed that 4-shogaol's antibacterial action primarily involves disrupting the bacterial cell membrane and efflux pumps. It also exhibited significant anti-virulence effects by reducing biofilm development and repressing virulence factors production, effectively protecting mice against P. aeruginosa infection. Furthermore, when combined with antibiotics, 4-shogaol demonstrated synergistic effects, leading to reduced minimum inhibitory concentrations (MICs) against P. aeruginosa. Its anti-virulence properties were linked to its ability to disrupt bacterial quorum sensing (QS) mechanisms, as evidenced by its interaction with QS receptors and downregulation of QS-related genes. Notably, in silico analysis indicated that 4-shogaol exhibited strong binding affinity to different P. aeruginosa QS targets. CONCLUSION: These findings suggest that 4-shogaol holds promise as an effective anti-virulence agent that can be utilized in combination with antibiotics for treating severe infections caused by gram-positive bacteria.

Ethnomedicinal uses, phytochemistry, and pharmacological relevance of Justicia procumbens (Oriental Water Willow) - A promising traditional plant.

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia procumbens L. (JP) (Oriental Water Willow, Shrimp plant, Acanthaceae) is a herbaceous plant that is commonly found in India, Taiwan, Australia, Southern China, Vietnam, and Korea. The plant has been primarily used to treat fever, asthma, edema, cough, jaundice, urinary tract infection, and sore throat, as well as for snake bites and as a fish-killer. In the present review, the reported phyto-chemical, ethno-pharmacological, biological, and toxicological studies on J. procumbens were summarized. Special focus had been given to its reported lignans, regarding their isolation, characterization, quantitative estimation, and biosynthesis. MATERIALS AND METHODS: A survey of the literature was done using assorted databases and publishers; Scopus, Sci-Finder, Web of Science, PubMed, GoogleScholar, ScienceDirect, Wiley, Taylors&Francis, Bentham, Thieme, and Springer. RESULTS: Currently, 95 metabolites have been separated fromJ. procumbens. Lignans and their glycosides were reported as main phyto-constituents of J. procumbens. Various methods are mentioned for quantitative estimation of these lignans. These phyto-constituents possessed wide pharmacological effectiveness, such as antiplatelet aggregation, antimicrobial, antitumor, and antiviral. CONCLUSIONS: Many of the stated effects are harmonious with the reported traditional uses of this plant. This data could further support J. procumbens's utilization as a herbal remedy and drug lead. However, further study of J. procumbens toxicity, as well as preclinical and clinical investigation is required to ensure the safe usage of J. procumbens.

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics.

Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (MPRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand-target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 MPRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 MPRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 MPRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC50/IC50 = 1.33 and CC50/IC50 = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC50/IC50 = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC50/IC50 = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 MPRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19.

Ethnobotanical Uses, Phytochemical Composition, Biosynthesis, and Pharmacological Activities of Carpesium abrotanoides L. (Asteraceae).

Carpesium abrotanoides L. (Asteraceae) is a medicinal plant with immense therapeutic importance and bioactivities. It is commonly encountered in various Asian regions. It has numerous ethnomedicinal uses for curing diverse ailments such as toothache, stomach ulcer, boils, tonsillitis, bronchitis, bacterial infection, bruises, swelling, virus infection, fever, and amygdalitis, as well as an anthelmintic versus round-, tape-, hook-, and pinworms. Different classes of phytoconstituents such as sesquiterpenes, sesquiterpene dimers, monoterpenes, and nitrogenous compounds have been reported from this plant. These phytoconstituents have proved to possess anti-inflammatory, cytotoxic, antimicrobial, and insecticidal capacities. The present review aims to summarize all published data on C. abrotanoides including traditional uses, phytoconstituents, bioactivities, and toxicological aspects, as well as the synthesis and biosynthesis of its metabolites through an extensive survey on various databases and various publishers. These reported data could draw the attention of various natural-metabolite-interested researchers and medicinal chemists towards the development of this plant and/or its metabolites into medicine for the prevention and treatment of certain illnesses. Despite the diverse traditional uses of C. abrotanoides, there is a need for scientific evidence to support these claims. Clinical trials are also required to further assure these data and validate this plant utilization in treating several diseases.

Lansium domesticum-A Fruit with Multi-Benefits: Traditional Uses, Phytochemicals, Nutritional Value, and Bioactivities.

Lansium domesticum (Langsat, Meliaceae) is a tropical fruit mainly found in Southeast Asian countries, particularly in Thailand, Malaysia, Indonesia, and the Philippines. Traditionally, it is utilized as a folk treatment for eye inflammation, ulcers, diarrhea, dysentery, fever, spasms, flatulence, worms, insect bites, scorpion stings, and malaria. Additionally, it is utilized as a mosquito repellent, skin moisturizer and whitening agent. Pharmacological research showed that the plant has a wide array of bioactivities, including antimalarial, antifeedant, anti-aging, wound healing, antioxidant, cytotoxic, analgesic, antibacterial, antimutagenic, insecticidal, and larvicidal. The most commonly described activities were attributed to the presence of terpenoids and phenolics. Further, some studies reported the preparation of nanoparticles and pharmaceutical formulations from the plant. This review highlights the potential of L. domesticum as herbal medicine. It provides an overview about the reported data on L. domesticum from 1931 to November 2021, including nutritional value, traditional uses, phytoconstituents, and bioactivities, as well as nanoparticles and pharmaceutical formulations.

Genus Salsola: Chemistry, Biological Activities and Future Prospective-A Review.

The genus Salsola L. (Russian thistle, Saltwort) includes halophyte plants and is considered one of the largest genera in the family Amaranthaceae. The genus involves annual semi-dwarf to dwarf shrubs and woody tree. The genus Salsola is frequently overlooked, and few people are aware of its significance. The majority of studies focus on pollen morphology and species identification. Salsola has had little research on its phytochemical makeup or biological effects. Therefore, we present this review to cover all aspects of genus Salsola, including taxonomy, distribution, differences in the chemical constituents and representative examples of isolated compounds produced by various species of genus Salsola and in relation to their several reported biological activities for use in folk medicine worldwide.

Anti-Proliferative, Cytotoxic and Antioxidant Properties of the Methanolic Extracts of Five Saudi Arabian Flora with Folkloric Medicinal Use: Aizoon canariense, Citrullus colocynthis, Maerua crassifolia, Rhazya stricta and Tribulus macropterus.

Saudi Arabian flora have a history of use as folklore remedies, although such properties have yet to be explored rigorously, and the safety of such remedies should be assessed. This study determined the anti-proliferative, cytotoxic, and antioxidant properties of extracts of the following five plants indigenous to Saudi Arabia: Aizoon canariense, Citrullus colocynthis, Maerua crassifolia, Rhazya stricta, and Tribulus macropterus. The aerial parts of the five plants were collected from various locations of the western and northern regions of Saudi Arabia and used to prepare methanolic extracts. Three approaches were used to determine the proliferation and cytotoxicity effects using HaCaT cells: MTT, FACS, and confocal microscopy. Meanwhile, two approaches were used to study the antioxidant potential: DPPH (acellular) and RosGlo (cellular, using HaCaT cells). C. colocynthis possessed anti-proliferative activity against HaCaT cells, showing a significant decrease in cell proliferation from 24 h onwards, while R. stricta showed significant inhibition of cell growth at 120 and 168 h. The IC50 values were determined for both plant extracts for C. colocynthis, with 17.32 and 16.91 µg/mL after five and seven days of treatment, respectively, and for R. stricta, with 175 and 105.3 µg/mL after five and seven days of treatment. R. stricta and M. crassifolia exhibited the highest capacities for scavenging the DPPH radical with IC50 values of 335 and 448 µg/mL, respectively. The subsequent ROS-Glo H2O2 assay confirmed these findings. The R. stricta and M. crassifolia extracts showed potent antioxidant activity in both acellular and cellular models. The C. colocynthis extract also demonstrated significant anti-proliferation and cytotoxic activity, as did the R. stricta extract. These properties support their usage in folk medicine and also indicate a further potential for development for holistic medicinal use or as sources of new active compounds.

Kirenol: A promising bioactive metabolite from siegesbeckia species: A detailed review.

ETHNOPHARMACOLOGICAL RELEVANCE: Kirenol (Kr) is an ent-pimarane type diterpenoid that has been reported from Siegesbeckiaorientalis, S. pubescens, and S. glabrescens (family Asteraceae). These plants have been used traditionally for treating various ailments such as hypertension, neurasthenia, rheumatoid arthritis, asthma, snakebites, allergic disorders, paralysis, soreness, cutaneous disorders, rubella, menstrual disorders, numbness of limbs, dizziness, headache, and malaria. Importantly, in recent years, Kr has received great attention due to its diversified pharmacological activities. AIM OF THE STUDY: The current work aims to give an overview on the reported pharmacological activities of Kr. Furthermore, the findings regarding its methods for extraction, quantitative analysis, purification, pharmacokinetics, pharmaceutical and food preparations, biosynthesis, identification, semisynthetic analogues, and toxicity are highlighted to provide a reference and perspective for its further investigation. METHODS: Electronic databases including ScienceDirect, Web of Knowledge, SCOPUS, Wiley Online Library, Taylor & Francis, PubMed, Springer, JACS, and Google Scholar were searched up to the beginning of 2021 to identify the reported studies. RESULTS: A total of 93 articles have been reviewed. The reported data suggested that Kr possessed various bioactivities including cytotoxic, apoptotic, anticancer, anti-inflammatory, cardio-protective, anti-photo-aging, anti-adipogenic, antimicrobial, muscle function improvement, fracture and wound healing, and anti-arthritic. In addition, studies revealed that the antioxidative and anti-inflammatory activities of Kr may mediate many of its therapeutic potentials as confirmed by several in-vitro and in-vivo studies. CONCLUSION: This review provides an updated summary of the recent studies on Kr, including methods for extraction, quantitative analysis, purification, pharmacokinetics, pharmaceutical and food preparations, biosynthesis, and identification, as well as semisynthetic analogues, pharmacological activities, and toxicity. Thus, this work can provide useful considerations for planning and design future research on Kr.

Osteoprotective Activity and Metabolite Fingerprint via UPLC/MS and GC/MS of Lepidium sativum in Ovariectomized Rats.

Lepidium sativum seeds are used traditionally to accelerate healing of bone fracture in addition to its culinary uses. This study aimed to characterize the osteoprotective effect of L. sativum in an ovariectomized rat model at two dose levels (50 and 100 mg/kg) using 17ß-estradiol as a positive reference standard. Moreover, a complete metabolite profile of L. sativum via UHPLC/PDA/ESI-MS, as well as headspace solid-phase microextraction (SPME)-GC/MS is presented. Results revealed that L. sativum extract exhibited significant anti-osteoporotic actions as evidenced by mitigating the decrease in relative bone weight concurrent with improved longitudinal and perpendicular femur compression strength. Further, the extract enhanced the serum bone formation biomarkers lactate dehydrogenase (LDH) activity and osteocalcin levels. The extract also inhibited exhaustion of superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) activities and accumulation of lipid peroxides in bone tissues. This is in addition to ameliorating the rise in the markers of bone resorption carboxyterminal telopeptide, type I (CTXI) and tartrate-resistant acid phosphatase (TRAP) and modulating receptor activator of nuclear factor kappa-Β ligand (RANKL)/ osteoprotegerin (OPG) expression. Metabolite characterization suggests that glucosinolates, lignans, coumarins, phenolic acids, and alkaloids mediate these anti-osteoporotic effects in a synergistic manner.

Major flavonoids from Psiadia punctulata produce vasodilation via activation of endothelial dependent NO signaling.

Vasodilators are important pharmacologic agents for managing and/or treating hypertension. Medicinal plants are considered as valuable source of bioactive compounds. We used a bioguided approach to isolate, identify, and investigate the possible vasodilation activities and mechanism(s) of the prepared methanol extract from aerial parts of Psiadia punctulata (MAPP), its bioactive fraction and active compounds. Vascular effects of MAPP were studied using isolated artery technique in the presence or absence of specific candidate pathways inhibitors, and found to produce a significant vasodilation of phenylephrine preconstricted rat aortae. The bioactive chloroform fraction yielded five methoxylated flavonoids: umuhengerin (1), gardenin A (2), gardenin B (3), luteolin-3',4' -dimethyl ether (4), and 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (5). Metabolites 1, 4, and 5 produced a significant vasodilation. Removal of the endothelium significantly inhibited MAPP vasodilation. Nitric oxide synthase inhibition and not prostacycline inhibition or K+ channel blocking, was found to cause the observed vasodilation inhibition. Both guanylate cyclase and adenylate cyclase inhibitions markedly inhibited MAPP vasodilation. In conclusion MAPP possesses vasodilation activities that is mediated through endothelial nitric oxide pathway, calcium dependent endothelial nitric oxide synthase activation, and interference with the depolarization process through calcium channel blocking activity.

Perisomalien A, a new cytotoxic scalarane sesterterpene from the fruits of Periploca somaliensis.

The CHCl3 fraction of MeOH extract of Periploca somaliensis (family Asclepiadaceae) fruits afforded a new scalarane sesterterpene, namely perisomalien A (1), along with lupeol acetate (2), ß-amyrin (3), cycloart-23Z-ene-3ß,25-diol (4), and ß-sitosterol-3-O-ß-D-glucopyranoside (5). Their chemical structures were established by various spectroscopic analyses, in addition to comparison with the formerly reported data. Moreover, the cytotoxic activity of these metabolites was assessed towards MCF-7, HepG2, and HCT-116 tumour cell lines using sulforhodamine B (SRB) assay. Compound 4 showed the most potent cytotoxic profile with IC50 9.0 µM towards MCF-7, compared to doxorubicin (IC50 0.18 µM). Also, 1 and 4 possessed the most potent effect towards HepG2 with IC50s 26.7 and 25.9 µM, respectively. In addition, all tested compounds showed cytotoxic effects with IC50 values ranging from 19.9 to 39.3 µM against HCT-116.

Natural Peroxisome Proliferator-Activated Receptor γ (PPARγ) Activators for Diabetes.

CONTEXT: Metabolic syndrome (MetS) represents a worldwide problem. Drugs used in MetS target different symptoms, like excessive body weight, insulin resistance, hyperglycemia, dyslipidemia, or hypertension. Peroxisome proliferator-activated receptors (PPAR) regulate the gene expression involved in lipid metabolism, inflammation, and adipogenesis. Activation of PPARγ has become a target of interest to counter hyperglycemia linked with MetS and type 2 diabetes (T2DM). OBJECTIVE: The current review intended to summarize reported research on medicinal plants, or their bioactive constituents, with PPARγ-activating potential. DESIGN: The research team searched the literature up to 2016 using electronic databases- ScienceDirect, PubMed, Google-Scholar, SpringerLink, Scopus, and Wiley-for publications on medicinal plants with promising PPARγ modulators using keywords diabetes mellitus, natural products, peroxisome proliferator-activated receptors, metabolic syndrome, adipogenesis. SETTING: This study was conducted in the Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia, Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt, and Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah, Al Munawwarah, Saudi Arabia. RESULTS: Several natural products were considered to be good ligands for PPARγ. The PPARγ agonistic activity of over 100 plants covered in this review was supported by experimental evidence. Some of the plants and their constituents had been studied for their possible mechanisms of action. CONCLUSIONS: Findings discussed in this review highlighted PPARγ's role as an organizer of lipid metabolism and glucose homeostasis, thus supporting its function as a target for antidiabetic agents. The discovery that some natural compounds and plants could activate PPARγ opens up the prospect for future development of strategies to take advantage of its therapeutic potential in diabetes. Therefore, the current review could provide significant information for biotechnological or pharmaceutical applications in targeted drug delivery and design.

Mentha longifolia alleviates experimentally induced angina via decreasing cardiac load.

Angina occurs due to imbalance between heart oxygen demand and supply and is associated with serious morbidity and mortality. Here, the possible antianginal effect of Mentha longifolia extract was studied in experimental model of angina. Aerial parts of M. longifolia were extracted, standardized, and given to rats three days before angina. Heart hemodynamics and conductivity were recorded by microtip catheter and surface electrodes. M. longifolia extract significantly alleviated the sustained decline in cardiac contractility after vasopressin exposure. However, M. longifolia did not affect the impaired cardiac dilation after vasopressin. Heart rate was significantly decreased after vasopressin exposure in rats treated with M. longifolia compared with untreated animals. In addition, M. longifolia produced more increase in systolic and diastolic durations after vasopressin exposure compared with untreated animals. Moreover, the plant extract alleviated the ST height changes during vasopressin injection. M. longifolia extract alleviates impaired cardiac function associated with angina through decreasing heart work. PRACTICAL APPLICATIONS: The present study is the first to study the effect of M. longifolia in an experimental model of angina. M. longifolia alleviated the impaired cardiac contractility associated with angina exposure. The antianginal effect of M. longifolia could be through reducing cardiac load. This can be concluded from the decrease in heart rate and the systolic and diastolic cycles elongation after exposure to vasopressin in animals pretreated with M. longifolia. This helps in reducing the associated cardiac ischemia upon exposure to vasopressin as indicated by ST change. This could provide new directions in the management of the serious angina disease.

Mangostanaxanthone VIII, a new xanthone from Garcinia mangostana and its cytotoxic activity.

A new prenylated xanthone, mangostanaxanthone VIII (7) and six known metabolites: gartanin (1), 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), rubraxanthone (3), 1,3,6,7-tetrahydroxy-8-prenylxanthone (4), garcinone C (5), and xanthone I (9-hydroxycalabaxanthone) (6) were separated from the EtOAc-soluble fraction of the air-dried pericarps of Garcinia mangostana (Clusiaceae). Their structures have been verified on the basis of spectroscopic data analysis as well as comparison with the literature. The cytotoxic activity of 7 was assessed against MCF7, A549, and HCT116 cell lines using sulforhodamine B (SRB) assay. Compound 7 showed significant cytotoxic potential against MCF7 and A549 cell lines with IC50s 3.01 and 1.96 µM, respectively compared to doxorubicin (0.06 and 0.44 µM, respectively). However, it exhibited moderate activity towards HCT116 cell line.

Cytotoxic constituents from Vicia monantha subsp. monantha seeds.

Chemical investigation of Vicia monantha subsp. monantha Retz. revealed isolation of one new hydroxy- fatty acid (6) identified as (6-Z, 10-E)-9-hydroxy henicosa-6,10-dienoic acid in addition to six known metabolites; hexadecanoic acid (1), ß-sitosterol (2), ß-amyrin (3), ß-sitosterol-glucoside (4), 2,3-dihydroxypropyl tetradecanoate (5) and (Z)-9-hydroxypentadec-6-enoic acid (7). The cytotoxic effect of the isolated compounds was assessed by MTT assay using lung cancer A-549, prostate cancer PC3, breast cancer MCF-7, colon cancer HCT-116 and liver cancer HepG2 cell lines. Only compounds 1, 2, and 4 showed cytotoxic effect on HCT-116 cells where compound 2 was the most active with IC50 value of 22.61 µg/mL. In addition, compounds 1, 2, 3, and 4 showed promising cytotoxic effect on MCF-7 cells with IC50 values of 21.03, 15.42, 10.089, and 11.34 µg/mL, respectively.

PPARα and γ Activation Effects of New Nor-triterpenoidal Saponins from the Aerial Parts of Anabasis articulata.

Anabasis articulata, traditionally used to treat diabetes, is rich in saponin content. This study was performed to investigate the agonistic effect of its saponins on peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in human hepatoma (HepG2) cells to explore the possibility of the involvement of these nuclear receptors in the mechanism of the antidiabetic effect of the plant. Chemical investigation of the n-butanol fraction resulted in the isolation of three new and one known 30-noroleanane triterpenoid saponins. The structures of the new compounds were elucidated as 3ß-hydroxy,23-aldehyde-30-norolean-12,20(29)-dien-28-oic acid-28-O-ß-D-glucopyranosyl ester (1: ), 3ß-O-D-galactopyranosyl-23-aldehyde-30-norolean-12,20(29)-dien-28-oic acid-28-O-ß-D-glucopyranosyl ester (2: ), and 3ß-O-D-xylopyranosyl-30-norolean-12,20(29)-dien-28-oic acid 28-O-ß-D-glucopyranosyl ester (3: ), while the known 30-nortriterpenoidal saponin was identified as boussingoside E (4: ). Although, the isolated saponins (1:  - 4: ) did not show > 1.5-fold activation of peroxisome proliferator-activated receptor-γ, but two of them (1: and 3: ) activated peroxisome proliferator-activated receptor-α to the higher extents of 2.25- and 1.86-fold, respectively. These results suggest that the reported antidiabetic action of the isolated saponins may not solely involve the activation of peroxisome proliferator-activated receptor-γ. However, the agonistic activity of the n-butanol fraction of A. articulata (1.71-fold induction) and two of its saponins (1: and 3: ) towards peroxisome proliferator-activated receptor-α may be beneficial in the cardiovascular condition that is closely associated with diabetes and other metabolic disorders.

Protective activity of tovophyllin A, a xanthone isolated from Garcinia mangostana pericarps, against acetaminophen-induced liver damage: role of Nrf2 activation.

Garcinia mangostana L. (GM, family Guttiferae) is one of the most widely recognized tropical fruits. GM is a wealthy pool of xanthones that exhibit a wide range of bioactivities. Tovophyllin A (TA) separated from GM pericarps was tested for its efficacy to ameliorate acetaminophen (APAP)-induced liver injury. Mice were injected with a single dose of APAP with or without TA pretreatment. The protective effects of TA against APAP-induced liver damage were evident through amelioration of serum indices of hepatotoxicity and improvement of hepatic histopathologic lesions. TA has antioxidant activity because it inhibited APAP-induced lipid peroxidation and improved the antioxidant capacity of the liver. Also, TA enhanced the mRNA expression of nuclear erythroid-related factor 2 (Nrf2) and its target genes. Protein expression of Nrf2 and heme oxygenase-1 was enhanced remarkably in TA-pretreated groups. TA suppressed activation of nuclear factor-kappa B (NF-κB) and the subsequent release of pro-inflammatory cytokines. In conclusion, TA has a marked protective activity against APAP-induced hepatotoxicity which may be linked to its ability to activate Nrf2 and inhibit the NF-κB signaling pathway.

Phenolics from Barleria cristata var. Alba as carcinogenesis blockers against menadione cytotoxicity through induction and protection of quinone reductase.

BACKGROUND: There are increasing interests in natural compounds for cancer chemoprevention. Blocking agents represent an important class of chemopreventive compounds. They prevent carcinogens from undergoing metabolic activation and thereby suppressing their interaction with cellular macromolecular targets. METHODS: The effect of phenolic compounds isolated from Barleria cristata var. alba as chemopreventive agent was evaluated. The ethyl acetate fraction of B. cristata was subjected to different chromatographic techniques for isolation of its major phenolic compounds. The isolated compounds were evaluated for their potential to induce the cancer chemopreventive enzyme marker NAD(P)H quinonereductase 1 (NQO1) in murine Hepa-1c1c7 cell model. RESULTS: The ethyl acetate fraction of B. cristata var. alba yielded five known compounds identified as verbascoside (1), isoverbascoside (2), dimethoxyverbascoside (3), p-hydroxy benzoic acid (4), and apigenin-7-O-glucoside (5). Among the tested compounds, isoverbascoside (2) was shown to potently induce the activity of the enzyme in a dose -dependent manner. As a functional assay for detoxification, compound 2 was the strongest to protect Hepa-1c1c7 against the toxicity of menadione, a quinone substrate for NQO1. CONCLUSION: This effect seemed to be attributed to the compound's potential to induce both the catalytic activity and protein expression of NQO1 as revealed by enzyme assay and Western blotting, respectively.

Saudi plants as a source of potential ß-lactamase inhibitors.

This study was performed to assess the potential ß-lactamase inhibitory properties of nineteen crude Saudi plant extracts belonging to eight families against extended spectrum ß-lactamase (ESßL) strains of Klebsiella pneumoniae and other medically important pathogens. A total of 276 microbial isolates of pathogenic bacteria were used in this study; only 15 of them showed decreased sensitivity to one or several of ceftazidime, aztreonam, cefotaxime or ceftriaxone, which are deemed to be possible producers of ESßL. Antibacterial activities of plant extracts were carried out against ESßL positive isolates by the disc diffusion method. The potential ESßL suppressing activities of plant extracts and prepared fractions, (chloroform and methanol), with or without antibiotic were studied by disc diffusion method. Results revealed that selected plant extracts showed no antibacterial activity against tested strains; meanwhile, only Echinops viscosus, Pulicaria arabica, Tephrosia nubica, Chrozophora oblongifolia, and Clutia myricoides showed pronounced ESßL inhibitory activities. The extracts were quantified for phenolic compounds and their antioxidant properties. Bio-guided fractionation of the active extracts revealed that the chloroform fraction of C. myricoides possess a promising ESßL inhibitory activity. The separation and the structural elucidation of the active compounds from C. myricoides will offer beneficial leads for developing ß-lactamase inhibitors.

Thiotagetin B and tagetannins A and B, new acetylenic thiophene and digalloyl glucose derivatives from Tagetes minuta and evaluation of their in vitro antioxidative and anti-inflammatory activity.

The three new metabolites: thiotagetin B (2) [(Z)-1″-([2,2'-bithiophen]-5-yl)-8″-chloro-6″,11″-dimethylundeca-6″,10″-dien-2″-yn-9″-one], tagetannin A (9) [3,4-bis-(galloyl-3,5-dimethyl ether)-(α/ß)-d-glucopyranose], and tagetannin B (10) [2,3-bis-(galloyl-3,5-dimethyl ether)-(α/ß)-d-glucopyranose], along with ecliptal (5-formyl-α-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2'-bithiophene (3), scopoletin (4), p-hydroxybenzoic acid (5), protocatechuic acid methyl ester (6), gallic acid (7), and patuletin 7-O-ß-d-glucoside (8) were isolated from the aerial parts of Tagetes minuta L. (Asteraceae). Their structures were verified by extensive spectroscopic analyses as well as by comparison with literature data. The isolated compounds were evaluated for their antioxidant and anti-inflammatory activities using DPPH and enzyme-linked immunosorbent assays, respectively. Compounds 5-10 possessed the highest antioxidant potential with a scavenging activity (SCA)≈74 to 93% of DPPH radicals. Moreover, 5-10 displayed significant anti-inflammatory potential, while 4 showed moderate activity. Compounds 5-10 exhibited significant decreases in NFκB p65, TNF-α, and IL-6 levels at all tested concentrations.