Self-assembled renewable nano-sized pentacyclic triterpenoid maslinic acids in aqueous medium for anti-leukemic, antibacterial and biocompatibility studies: An insight into targeted proteins-compound interactions based mechanistic pathway prediction through molecular docking.

Maslinic acid is a naturally occurring dihydroxy, mono-carboxy bioactive triterpenoid. Its bulky structure was the main hindrance in the path of biological activity. Sodium and potassium salts of nano-sized triterpenoid maslinic acid were prepared from maslinic acid and its self-assembly property was studied in aqueous and aqueous-organic binary liquid mixtures. Morphology of the compounds studied by Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), High Resolution Transmission Electron Microscopy (HRTEM), Optical Microscopy, Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) revealed vesicular morphology of the self-assemblies. Selective cytotoxicity was performed in leukemic (K-562 and KG-1a) and PBMC cells. Among the three self-assemblies (maslinic acid 1, sodium maslinate 2 and potassium maslinate 3), sodium maslinate 2 showed better antileukemic efficacy. Sodium maslinate 2 induced apoptosis in leukemic cells by elevating ROS levels and disrupting the cellular antioxidant system. From the in-silico studies, it was confirmed that 2 interacted with extrinsic and intrinsic apoptotic proteins of leukemic cells and killed those cells by inducing apoptotic pathways. The compounds 1, 2 and 3 showed significant antibacterial efficacy against E.coli strain through binding with several periplasmic membrane fusion protein (MFP) and limiting the efflux system leading to arrestation of antimicrobial resistance.

Plectranthus zeylanicus: A Rich Source of Secondary Metabolites with Antimicrobial, Disinfectant and Anti-Inflammatory Activities.

Plectranthus zeylanicus Benth is used in Sri Lankan folk medicine as a remedy for inflammatory conditions and microbial infections. Our previous investigations revealed potent 5-lipoxygenase (5-LO) inhibitory activity in lipophilic extracts of this plant, supporting its anti-inflammatory potential. In-depth studies on the antimicrobial activity have not been conducted and the bioactive ingredients remained elusive. As a continuation of our previous work, the present investigation was undertaken to evaluate the antimicrobial activity of different extracts of P. zeylanicus and to isolate and characterize bioactive secondary metabolites. Different organic extracts of this plant were analyzed for their antibacterial activity, and the most active extract, i.e., dichloromethane extract, was subjected to bioactivity-guided fractionation, which led to the isolation of 7α-acetoxy-6ß-hydroxyroyleanone. This compound displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 62.5 µg/mL, and its disinfectant capacity was comparable to the potency of a commercial disinfectant. Moreover, 7α-acetoxy-6ß-hydroxyroyleanone inhibits 5-LO with IC50 values of 1.3 and 5.1 µg/mL in cell-free and cell-based assays, respectively. These findings rationalize the ethnopharmacological use of P. zeylanicus as antimicrobial and anti-inflammatory remedy.

The Anti-Inflammatory and Antimicrobial Potential of Selected Ethnomedicinal Plants from Sri Lanka.

Traditional folk medicine in Sri Lanka is mostly based on plants and plant-derived products, however, many of these medicinal plant species are scientifically unexplored. Here, we evaluated the anti-inflammatory and antimicrobial potency of 28 different extracts prepared from seven popular medicinal plant species employed in Sri Lanka. The extracts were subjected to cell-based and cell-free assays of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1, and nitric oxide (NO) scavenging activity. Moreover, antibacterial and disinfectant activities were assessed. Characterization of secondary metabolites was achieved by gas chromatography coupled to mass spectrometric (GC-MS) analysis. n-Hexane- and dichloromethane-based extracts of Garcinia cambogia efficiently suppressed 5-LO activity in human neutrophils (IC50 = 0.92 and 1.39 µg/mL), and potently inhibited isolated human 5-LO (IC50 = 0.15 and 0.16 µg/mL) and mPGES-1 (IC50 = 0.29 and 0.49 µg/mL). Lipophilic extracts of Pothos scandens displayed potent inhibition of mPGES-1 only. A methanolic extract of Ophiorrhiza mungos caused significant NO scavenging activity. The lipophilic extracts of G. cambogia exhibited prominent antibacterial and disinfectant activities, and GC-MS analysis revealed the presence of fatty acids, sesquiterpenes and other types of secondary metabolites. Together, our results suggest the prospective utilization of G. cambogia as disinfective agent with potent anti-inflammatory properties.

Development of Novel Topical Cosmeceutical Formulations from Nigella sativa L. with Antimicrobial Activity against Acne-Causing Microorganisms.

Acne vulgaris occurs due to the inflammation of sebaceous follicles in the skin. It is triggered by the activity of some bacterial species like Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis. Acquisition of antibiotic resistance by these microorganisms and adverse effects associated with the current treatment regimens necessitate the introduction of novel therapeutic agents for acne vulgaris. Thus, this study was undertaken to develop novel gel formulations from seeds of Nigella sativa L. and to evaluate the antibacterial potential against some acne-causing bacterial species. The antibacterial activity of seed extracts was initially screened against S. aureus and P. acnes by the agar well diffusion method. Thereafter, topical gels were formulated incorporating the ethyl acetate extract of seeds of N. sativa at three different concentrations. These topical formulations were subjected to antimicrobial activity studies while the stability was evaluated over a period of 30 days. All three formulations were capable of inhibiting the growth of S. aureus and P. acnes, with the highest antibacterial activity in the formulation comprising 15% of the seed extract. Interestingly, the antibacterial potency of this formulation against S. aureus surpassed the commercial synthetic product used as the positive control. Moreover, any alteration in color, odor, homogeneity, washability, consistency, and pH was not observed while the antibacterial potency was also retained during the storage period. The potent antibacterial activity in topical gel formulations developed from the ethyl acetate extract of N. sativa signposts their suitability as alternatives to existing antiacne agents in the management of acne vulgaris.

Traditional Uses of Medicinal Plants in Polonnaruwa District in North Central Province of Sri Lanka.

Sri Lanka harbors over 3000 plant species, and most of these plants have been of immense importance in the traditional systems of medicine in the country. Although there is a rich reserve of indigenous knowledge on medicinal plants, in-depth studies have not been pursued yet to compile the ethnoflora with traditional medicinal applications for the scientific community. Thus, as a continuation of our ethnobotanical inventory work in different regions in the country, the present study was carried out in one of the administrative districts in the North Central area of Sri Lanka known as Polonnaruwa district. The information on the significance of medicinal plants as curative and preventive agents of diseases was collected through semistructured and open-ended interviews from 284 volunteers who were randomly recruited for the study. Ethnobotanical data were analyzed using relative frequency of citation (RFC), family importance value (FIV), and use value (UV). Out of the total participants, 53.7% claimed the use of herbal remedies. A total of 64 medicinal plants belonging to 42 plant families were recorded, out of which Coriandrum sativum L. (RFC = 0.163) was the most cited species. Out of the 42 plant families recorded, the FIV was highest in Zingiberaceae. Coscinium fenestratum (Goetgh.) Colebr. was found as the plant with the highest use value. Furthermore, the majority of the nonusers of the herbal remedies were willing to adopt herbal products upon the scientific validation of their therapeutic potential. This study revealed that the indigenous herbal remedies are still popular among the local communities in the study area.

An Ethnobotanical Study of the Medicinal Plants Used as Anti-Inflammatory Remedies in Gampaha District, Western Province, Sri Lanka.

The application of traditional medicinal plants as anti-inflammatory remedies has been practiced in Sri Lanka for thousands of years. Although there is a rich reserve of indigenous knowledge of medicinal plants, the preservation and the scientific validation of these claims are still in its infancy. Thus, the study was carried out in one of the administrative areas of Sri Lanka known as Gampaha District to assess the significance and contribution of medicinal plants in inflammatory conditions. The data were collected through semistructured and open-ended interviews from 458 volunteers. Ethnobotanical data were analyzed using the relative frequency of citation (RFC), family importance value (FIV), and use value (UV). Out of the total participants, 50.7% claimed the use of medicinal plants for the treatment of inflammatory conditions such as fever, cough, asthma, swellings, and pain in the joints. A total of 43 medicinal plants belonging to 28 plant families were mentioned, out of which Coriandrum sativum (RFC = 0.23) was the most cited species. The most cited plant family was Fabaceae, and the family importance value was highest in Apiaceae. The majority of the nonusers of the herbal remedies mentioned that they would shift to herbal products if scientific information is available on the efficacy of these products.

Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Leucas zeylanica (L.) W.T. Aiton is a popular, multi-purpose medicinal plant in Sri Lanka but the pharmacological potential and the chemical profile have not been systematically investigated to understand and rationalize the reported ethnobotanical significance. AIM OF THE STUDY: The present study was undertaken to scientifically validate the traditional usage of this plant for the treatment of inflammatory conditions, gout and microbial infections. Inhibition of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1 and xanthine oxidase (XO) by different extracts of L. zeylanica was investigated to determine the anti-inflammatory and anti-gout activity, respectively. The antibacterial and antifungal activities were also studied and the relevant constituents in the bioactive extracts were tentatively identified. MATERIALS AND METHODS: Cell-free and/or cell-based assays were employed in order to investigate the effects of the extracts against the activity of human 5-LO, mPGES-1 and XO as well as to assess antioxidant properties. The antibacterial activity of the extracts was determined by the broth micro-dilution method against Gram positive and Gram negative bacteria including methicillin-resistant Staphylococcus aureus while the agar dilution method was employed to determine the anti-Candida activity. Gas chromatography coupled to mass spectrometric (GC-MS) analysis enabled the characterization of secondary metabolites in the extracts. RESULTS: The dichloromethane extract of L. zeylanica efficiently inhibited 5-LO activity in stimulated human neutrophils (IC50 = 5.5 µg/mL) and isolated human 5-LO and mPGES-1 (IC50 = 2.2 and 0.4 µg/mL). Potent inhibition of XO was observed by the same extract (IC50 = 47.5 µg/mL), which is the first report of XO-inhibitory activity of a Sri Lankan medicinal plant. Interestingly, significant radical scavenging activity was not observed by this extract. Only the n-hexane extract exhibited antibacterial activity against Staphylococcus aureus and Staphylococcus saprophyticus with a MIC of 250 µg/mL while the anti-Candida activity was moderate. GC-MS analysis revealed the presence of phytosterols, fatty acids, sesquiterpenes, diterpenes and several other types of secondary metabolites. CONCLUSIONS: Potent inhibition of 5-LO, mPGES-1 and XO rationalizes the ethnopharmacological use of L. zeylanica as anti-inflammatory and anti-gout remedy. Interestingly, the antimicrobial activities were not prominent, despite its wide utility as an antimicrobial medication.

Photoprotective potential in some medicinal plants used to treat skin diseases in Sri Lanka.

BACKGROUND: The constant exposure to solar ultraviolet radiation (UV) has a variety of harmful effects on human health. Although synthetic sunscreen products have been introduced as a preventive/therapeutic strategy, with the realization of their adverse side effects, the recent trend is to search for human friendly alternative formulations especially of plant origin. Therefore, the present study focuses on evaluation of photoprotective activity of aqueous extracts (1 mg/ml) of eleven medicinal plants in Sri Lanka that have been widely employed in traditional medicine as treatment options for various skin diseases and to improve the complexion. METHODS: For the determination of UV filtering potential of the extracts, UV absorption was measured and the sun protection factor (SPF) was calculated according the Mansur equation. The antioxidant activity was evaluated by DPPH and ABTS assays. RESULTS: Among the extracts, Atalantia ceylanica, Hibiscus furcatus, Leucas zeylanica, Mollugo cerviana, Olax zeylanica and Ophiorrhiza mungos have displayed SPF value ≥ 25, which are even higher than two commercial photoprotective creams used as reference compounds. L. zeylanica and O. mungos have displayed a high UV absorbance in 260-350 nm range indicating their potential of being broad spectrum sunscreens. In addition, the extract of O. mungos was found to be photostable, without any significant reduction in the SPF after exposure to direct solar radiation for 21 days. DPPH assay and the ABTS assay revealed that the extracts possess high antioxidant activity. CONCLUSION: The results of the present study suggest that the presence of secondary metabolites with antioxidant property could be responsible for the high UV absorbance. Our findings would offer an exciting avenue for further research towards the development of herbal cosmetics.

Preventing ragging: outcome of an integrated programme in a medical faculty in Sri Lanka.

Ragging is prevalent in higher educational institutes in Sri Lanka and the deaths of some new entrants in the past have been directly linked to physical and emotional torture caused by cruel acts of ragging. Although there are general anti-ragging rules in place, the effectiveness of these measures is unknown. We developed an action plan to prevent ragging by integrating the views of the major stakeholders, implemented the plan and assessed its success. This article highlights the action plan and its success in a medical faculty in southern Sri Lanka.

Munronia pinnata (Wall.) Theob.: unveiling phytochemistry and dual inhibition of 5-lipoxygenase and microsomal prostaglandin E2 synthase (mPGES)-1.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations from Munronia pinnata (Wall.) Theob. are extensively used in traditional medicine in Sri Lanka for the treatment of inflammatory conditions. However, neither the pharmacological features nor the phytochemistry of this plant are explored in order to understand and rationalize the reported ethnobotanical significance. As 5-lipoxygenase (5-LO) and microsomal prostaglandin E2 synthase (mPGES)-1 are crucial enzymes in inflammatory disorders, we evaluated their inhibition by M. pinnata extracts and studied the chemical profile of the plant for the identification of relevant constituents. MATERIALS AND METHODS: Cell-free and cell-based assays were employed in order to investigate the suppression of 5-LO and mPGES-1 activity. Cell viability, radical scavenger activities, and inhibition of reactive oxygen species formation (ROS) in neutrophils were studied to assess cytotoxic and antioxidant effects. Gas and liquid chromatography coupled to mass spectrometric analysis enabled the characterization of secondary metabolites. RESULTS: The n-hexane extract of M. pinnata efficiently suppressed 5-LO activity in stimulated human neutrophils (IC50 =8.7µg/ml) and potently inhibited isolated human recombinant 5-LO (IC50 =0.48µg/ml) and mPGES-1 (IC50 =1.0µg/ml). In contrast, no significant radical scavenging activity or suppression of ROS formation was observed, and neutrophil viability was unaffected. The phytochemistry of the plant was unveiled for the first time and phytosterols, fatty acids, sesquiterpenes and several other types of secondary metabolites were identified. CONCLUSIONS: Together, potent inhibition of 5-LO and mPGES-1 activity, without concomitant antioxidant activity and cytotoxic effects, rationalizes the ethnopharmacological use of M. pinnata as anti-inflammatory remedy. Detailed chromatographic/mass spectrometric analysis reveals discrete chemical structures of relevant constituents.

Inhibition of 5-lipoxygenase as anti-inflammatory mode of action of Plectranthus zeylanicus Benth and chemical characterization of ingredients by a mass spectrometric approach.

ETHNOPHARMACOLOGICAL RELEVANCE: The perennial herb Plectranthus zeylanicus Benth is extensively used in traditional medicine in Sri Lanka and South India for treating inflammatory conditions, but pharmacological features of Plectranthus zeylanicus are hardly explored in order to understand and rationalize its use in ethnomedicine. As 5-lipoxygenase (5-LO) is a key enzyme in inflammatory disorders such as asthma or atherosclerosis, we investigated 5-LO inhibition by Plectranthus zeylanicus extracts and analyzed relevant constituents. MATERIALS AND METHODS: We applied cell-free and cell-based assays to investigate suppression of 5-LO activity. Cell viability, radical scavenger activities, and inhibition of reactive oxygen species formation (ROS) in neutrophils were analysed to exclude unspecific cytotoxic or antioxidant effects. Constituents of the extracts were characterized by bioassay-guided fractionation and by analysis using gas or liquid chromatography coupled to mass spectrometric (Orbitrap) analysis. RESULTS: Extracts of Plectranthus zeylanicus prepared with n-hexane or dichloromethane potently suppressed 5-LO activity in stimulated human neutrophils (IC50=6.6 and 12µg/ml, respectively) and inhibited isolated human recombinant 5-LO (IC50=0.7 and 1.2µg/ml, respectively). In contrast, no significant radical scavenging activity or suppression of ROS formation was observed, and neutrophil viability was unaffected. Besides ubiquitously occurring ingredients, coleone P, cinncassiol A and C, and callistric acid were identified as constituents in the most active fraction. CONCLUSIONS: Together, potent inhibition of 5-LO activity, without concomitant anti-oxidant activity and cytotoxic effects, rationalizes the ethnopharmacological use of Plectranthus zeylanicus as anti-inflammatory remedy. Modern chromatographic/mass spectrometric analysis reveals discrete chemical structures of relevant constituents.

Azahelicene Superbases as MAILD Matrices for Acidic Analytes.

Fitting the profile: A superbasic 1,14-diaza[5]helicene can serve as an efficient, ionless matrix for matrix-assisted ionization/laser desorption (MAILD) spectrometry. The matrix outperforms other bases by acting as a kinetically active proton sponge and is highly suitable for high-throughput metabolomics analysis. There is a correlation between the basicity (and proton-sponge character) of matrices and their efficacy in MAILD-MS.