Burgeoning therapeutic strategies to curb the contemporary surging viral infections.

Significant efforts and initiatives were already made in the health care systems, however in the last few years; our world is facing emergences of viral infections which potentially leading to considerable challenges in terms of higher morbidity, mortality, increased and considerable financial loads on the affected populations. Over ten major epidemics or pandemics have been recorded in the twenty-first century, the ongoing coronavirus pandemic being one of them. Viruses being distinct obligate pathogens largely dependent on living beings are considered as one of the prominent causes of death globally. Although effective vaccines and antivirals have led to the eradication of imperative viral pathogens, the emergences of new viral infections as well as novel drug-resistant strains have necessitated the implementation of ingenious and efficient therapeutic approaches to treat viral outbreaks in the future. Nature being a constant source of tremendous therapeutical resources has inspired us to develop multi-target antiviral drugs, overcoming the challenges and limitations faced by pharmaceutical industry. Recent breakthroughs in the understanding of the cellular and molecular mechanisms of viral reproduction have laid the groundwork for potential treatment approaches including antiviral gene therapy relying on the application of precisely engineered nucleic acids for disabling pathogen replication. The development of RNA interference and advancements in genome manipulating tools have proven to be especially significant in this regard. In this review, we discussed mode of actions and pathophysiological events associated with the viral infections; followed by distributions, and advancement made towards the detection strategies for timely diagnosis. In the later section, current approaches to cope up the viral pathogens and their key limitations have also been elaborated. Lastly, we also explored some novel and potential targets to treat such infections, where attentions were made on next generation gene editing technologies.

NMR-Based Metabolomics: A New Paradigm to Unravel Defense-Related Metabolites in Insect-Resistant Cotton Variety through Different Multivariate Data Analysis Approaches.

Cotton (Gossypium hirsutum) is an economically important crop and is widely cultivated around the globe. However, the major problem of cotton is its high vulnerability to biotic and abiotic stresses. It has been around three decades since the cotton plant was genetically engineered with genes encoding insecticidal proteins (mainly Cry proteins) with an aim to protect it against insect attack. Several studies have been reported on the impact of these genes on cotton production and fiber quality. However, the metabolites responsible for conferring resistance in genetically modified cotton need to be explored. The current work aims to unveil the key metabolites responsible for insect resistance in Bt cotton and also compare the conventional multivariate analysis methods with deep learning approaches to perform clustering analysis. We aim to unveil the marker compounds which are responsible for inducing insect resistance in cotton plants. For this purpose, we employed 1H-NMR spectroscopy to perform metabolite profiling of Bt and non-Bt cotton varieties, and a total of 42 different metabolites were identified in cotton plants. In cluster analysis, deep learning approaches (linear discriminant analysis (LDA) and neural networks) showed better separation among cotton varieties compared to conventional methods (principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLSDA)). The key metabolites responsible for inter-class separation were terpinolene, α-ketoglutaric acid, aspartic acid, stigmasterol, fructose, maltose, arabinose, xylulose, cinnamic acid, malic acid, valine, nonanoic acid, citrulline, and shikimic acid. The metabolites which regulated differently with the level of significance p < 0.001 amongst different cotton varieties belonged to the tricarboxylic acid cycle (TCA), Shikimic acid, and phenylpropanoid pathways. Our analyses underscore a biosignature of metabolites that might involve in inducing insect resistance in Bt cotton. Moreover, novel evidence from our study could be used in the metabolic engineering of these biological pathways to improve the resilience of Bt cotton against insect/pest attacks. Lastly, our findings are also in complete support of employing deep machine learning algorithms as a useful tool in metabolomics studies.

Centella asiatica (L.) Urb. Extract ameliorates branched-chain amino acid (BCAA) metabolism in acute reserpine-induced stress zebrafish model via 1H Nuclear Magnetic Resonance (NMR)-based metabolomics approach.

Depression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.

Metabolites in Conocarpus erectus leaves attenuate α-amylase activity by modulating amino acid residues of α-amylase: an in vitro and docking study / Los metabolitos en las hojas de Conocarpus erectus atenúan la actividad de la α-amilasa al modular los residuos de aminoácidos de la α-amilasa: un estudio in vitro y de acoplamiento

The antioxidant activity and the inhibitory potential of α-amylase of lyophilized hydroethanolic extracts of Conocarpus erectus leaves obtained by ultrasonication were determined. The most potent extract was subjected to ultra-high performance liquid chromatography system equipped with mass spectrometer for metabolite identification. The identified metabolites were docked in α-glucosidase to assess their binding mode. The results revealed that 60% ethanolic extract exhibited highest ferric reducing antioxidant power (4.08 ± 0.187 mg TE/g DE) and α-amylase inhibition (IC50 58.20 ± 1.25 µg/mL. The metabolites like ellagic acid, 3-O-methyl ellagic acid, ferujol, 5, 2 ́-dihydroxy-6,7,8-trimethyl flavone and kaempferol glucoside were identified in the extract and subjected to molecular docking studies regarding α-amylase inhibition. The comparison of binding affinities revealed 3-O-methyl ellagic acid as most effective inhibitor of α-amylase with binding energy of -14.5911 kcal/mol comparable to that of acarbose (-15.7815 kcal/mol). The secondary metabolites identified in the study may be extended further for functional food development with antidiabetic properties.

Se determinó la actividad antioxidante y el potencial inhibidor de la α-amilasa de extractos hidroetanólicos liofilizados de hojas de Conocarpus erectus obtenidos por ultrasónicación. El extracto más potente se sometió a un sistema de cromatografía líquida de ultra alto rendimiento equipado con un espectrómetro de masas para la identificación de metabolitos. Los metabolitos identificados se acoplaron en α-glucosidasa para evaluar su modo de unión. Los resultados revelaron que el extracto etanólico al 60% exhibió el mayor poder antioxidante reductor férrico (4.08 ± 0.187 mg TE/g DE) e inhibición de la α-amilasa (IC50 58.20 ± 1.25 µg/mL. Los metabolitos como el ácido elágico, 3-O-metil elágico ácido, ferujol, 5, 2 ́-dihidroxi-6,7,8-trimetil flavona y kaempferol glucósido se identificaron en el extracto y se sometieron a estudios de acoplamiento molecular con respecto a la inhibición de la α-amilasa. La comparación de las afinidades de unión reveló 3-O-metil El ácido elágico como inhibidor más eficaz de la α-amilasa con una energía de unión de -14,5911 kcal/mol comparable a la de la acarbosa (-15,7815 kcal/mol). Los metabolitos secundarios identificados en el estudio pueden ampliarse aún más para el desarrollo funcional de alimentos con propiedades antidiabéticas.

1H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken, Chevon, Beef and Donkey Meat.

Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat. This work aimed to differentiate different meat samples on the basis of metabolites. The metabolic difference between various meat samples was investigated through Nuclear Magnetic Resonance spectroscopy coupled with multivariate data analysis approaches like principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). In total, 37 metabolites were identified in the gluteal muscle tissues of cow, goat, donkey and chicken using 1H-NMR spectroscopy. PCA was found unable to completely differentiate between meat types, whereas OPLS-DA showed an apparent separation and successfully differentiated samples from all four types of meat. Lactate, creatine, choline, acetate, leucine, isoleucine, valine, formate, carnitine, glutamate, 3-hydroxybutyrate and α-mannose were found as the major discriminating metabolites between white (chicken) and red meat (chevon, beef and donkey). However, inosine, lactate, uracil, carnosine, format, pyruvate, carnitine, creatine and acetate were found responsible for differentiating chevon, beef and donkey meat. The relative quantification of differentiating metabolites was performed using one-way ANOVA and Tukey test. Our results showed that NMR-based metabolomics is a powerful tool for the identification of novel signatures (potential biomarkers) to characterize meats from different sources and could potentially be used for quality control purposes in order to differentiate different meat types.

Cassia fistula Leaves; UHPLC-QTOF-MS/MS Based Metabolite Profiling and Molecular Docking Insights to Explore Bioactives Role Towards Inhibition of Pancreatic Lipase.

The present work was aimed at investigating hydroethanolic leaf extracts of Cassia fistula for their antioxidant and pancreatic lipase (PL) enzyme inhibitory properties. The most active extract was selected to profile the phytoconstituents by UHPLC-QTOF-MS/MS technique. Among the tested extracts, the 80% hydroethanolic extract exhibited the maximum levels of total phenolic and flavonoid contents (TPC and TFC) with a contribution of 201.3 ± 2.6 mg of gallic acid equivalent per gram of extract (GAE/g extract), and 116.3 ± 2.4 mg of rutin equivalent per gram of extract (RE/g extract), respectively. The same extract also showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and PL inhibitory activity with an IC50 (half maximal inhibitory concentration) of 30.5 ± 2.8 µg/mL and 17.31 ± 1.18 µg/mL, respectively. The phytochemical profiling of 80% hydroethanolic extract confirmed the presence of 23 metabolites of immense medicinal significance. Docking studies were conducted to investigate the potential interactions of compounds identified in the study. The docking study-based binding energy data and the interaction scheme both revealed the possible role of the identified compounds towards PL inhibitor. Moreover, energies of frontier molecular orbitals (FMOs), ionization potentials (IP), electron affinities (EA) and molecular electrostatic potentials (MEP) were also explored. The findings of the current work suggest that C. fistula is a promising natural source of antioxidant and antiobesity agents, which may be exploited to add pharmacological functionalities to food.

Clitorienolactones and Isoflavonoids of Clitorea ternatea Roots Alleviate Stress-Like Symptoms in a Reserpine-Induced Zebrafish Model.

Clitorea ternatea has been used in Ayurvedic medicine as a brain stimulant to treat mental illnesses and mental functional disorders. In this study, the metabolite profiles of crude C. ternatea root extract (CTRE), ethyl acetate (EA), and 50% aqueous methanol (50% MeOH) fractions were investigated using ultrahigh-performance liquid chromatography-diode array detector-tandem mass spectrometry (UHPLC-DAD-MS/MS), while their effect on the stress-like behavior of zebrafish, pharmacologically induced with reserpine, was investigated. A total of 32 compounds were putatively identified, among which, a series of norneolignans, clitorienolactones, and various flavonoids (flavone, flavonol, isoflavone, and isoflavanone) was found to comprise the major constituents, particularly in the EA and 50% MeOH fractions. The clitorienolactones, presently unique to the species, were present in both the free and glycosylated forms in the roots. Both the EA and 50% MeOH fractions displayed moderate effects on the stress-induced zebrafish model, significantly decreasing freezing duration and elevating the total distance travelled and average velocity, 72 h post-treatment. The results of the present study provide further evidence that the basis for the use of C. ternatea roots in traditional medicine to alleviate brain-related conditions, such as stress and depression, is attributable to the presence of clitorienolactones and the isoflavonoidal constituents.

Recovery of Gelatin from Bovine Skin with the Aid of Pepsin and Its Effects on the Characteristics of the Extracted Gelatin.

Pepsin enzyme was used to pretreat the bovine skin at the rate of 5, 15, and 25 units of enzyme/g of skin to recover gelatin, and the recovered gelatins were referred to as Pe5, Pe15, and Pe25, respectively. The gelatin yield increased significantly (p < 0.05) from 18.17% for Pe5 to 24.67% for Pe25 as the level of pepsin increased, but the corresponding gel strength and viscosity decreased significantly (p < 0.05) from 215.49 to 56.06 g and 9.17 to 8.17 mPa·s for Pe5 and Pe25, respectively. ß- and α1- and α2-chains were degraded entirely in all the gelatins samples as observed in protein pattern elaborated by gel electrophoresis. 1H nuclear magnetic resonance (1H NMR) analysis indicated the coiled structure of gelatin protein chains. The lowest amide III amplitude of Pe25 as found by Fourier transform infrared (FTIR) spectroscopy indicated that α-helix structure of protein chains were lost to more irregular coiled structure. Thus, it could be summarized that pepsin might be used at the lower level (5 units/g of wet skin) to extract gelatin from bovine skin with good functional properties and at higher level (15/25 units/g of wet skin) to obtain gelatin of industrial grade with high yield.

Meat Quality, Fatty Acid Content and NMR Metabolic Profile of Dorper Sheep Supplemented with Bypass Fats.

The supplementation of rumen bypass fat (RBF) has remained one of the preferred approaches used to decrease undesirable saturated fatty acids (FA) and increase beneficial unsaturated FA in the meat. This study was planned to evaluate the influences of rumen bypass fats on meat quality, fatty acid and metabolic profiles in male Dorper sheep (n = 36) with 24.66 ± 0.76 kg (mean ± standard error) initial body weight. Treatment comprised a basal diet (30:70 rice straw to concentrate) with no added RBF as a control (CON), basal diet with prilled fat (PF), basal diet with prilled fat plus lecithin (PFL) and basal diet with calcium soap of palm fatty acids (CaS). The findings revealed that cooking loss, drip loss and shear force in longissimus dorsi (LD) muscle were not affected by RBF supplementation, while meat pH was significantly higher in the CaS on aging day 1. However, the diet supplemented with prilled fat and lecithin modified the meat's fatty acid profile significantly by increasing unsaturated fatty acids and decreasing saturated fats. The relative quantification of the major differentiating metabolites found in LD muscle of sheep showed that total cholesterol, esterified cholesterol, choline, glycerophosphocholine and glycerophospholipids were significantly lower in CaS and PFL diets, while glycerol and sphingomyelin were significantly higher in CaS and PFL diets. Most of the metabolites in the liver did not show any significant difference. Based on our results, the supplementation of protected fats did not have a negative influence on meat quality and the meat from Dorper sheep fed prilled fat with lecithin contained more healthy fatty acids compared to other diets.

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by 1H Nuclear Magnetic Resonance-Based Metabolomics.

Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), ß-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.

Anti-Obesity Attributes; UHPLC-QTOF-MS/MS-Based Metabolite Profiling and Molecular Docking Insights of Taraxacum officinale.

The naturopathic treatment of obesity is a matter of keen interest to develop efficient natural pharmacological routes for disease management with low or negligible toxicity and side effects. For this purpose, optimized ultrasonicated hydroethanolic extracts of Taraxacum officinale were evaluated for antiobesity attributes. The 2,2-diphenyl-1-picrylhydrazyl method was adopted to evaluate antioxidant potential. Porcine pancreatic lipase inhibitory assay was conducted to assess the in vitro antiobesity property. Ultra-high performance chromatography equipped with a mass spectrometer was utilized to profile the secondary metabolites in the most potent extract. The 60% ethanolic extract exhibited highest extract yield (25.05 ± 0.07%), total phenolic contents (123.42 ± 0.007 mg GAE/g DE), total flavonoid contents (55.81 ± 0.004 RE/g DE), DPPH-radical-scavenging activity (IC50 = 81.05 ± 0.96 µg/mL) and pancreatic lipase inhibitory properties (IC50 = 146.49 ± 4.24 µg/mL). The targeted metabolite fingerprinting highlighted the presence of high-value secondary metabolites. Molecular-binding energies computed by docking tool revealed the possible contribution towards pancreatic lipase inhibitory properties of secondary metabolites including myricetin, isomangiferin, icariside B4, kaempferol and luteolin derivatives when compared to the standard drug orlistat. In vivo investigations revealed a positive impact on the lipid profile and obesity biomarkers of obese mice. The study presents Taraxacum officinale as a potent source of functional bioactive ingredients to impart new insights into the existing pool of knowledge of naturopathic approaches towards obesity management.

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma.

Butea monosperma is one of the extensively used plants in traditional system of medicines for many therapeutic purposes. In this study, the antioxidant activity, α-glucosidase and α-amylase inhibition properties of freeze drying assisted ultrasonicated leaf extracts (hydro-ethanolic) of B. monosperma have been investigated. The findings revealed that 60% ethanolic fraction exhibited high phenolic contents, total flavonoid contents, highest antioxidant activity, and promising α-glucosidase and α-amylase inhibitions. The UHPLC-QTOF-MS/MS analysis indicated the presence of notable metabolites of significant medicinal potential including apigenin, apigenin C-hexoside C-pentoside, apigenin C-hexoside C-hexoside, apigenin-6,8-di-C-pentoside and genistin etc., in B. monosperma leave extract. Docking studies were carried out to determine the possible role of each phytochemical present in leaf extract. Binding affinity data and interaction pattern of all the possible phytochemicals in leaf extract of B. monosperma revealed that they can inhibit α-amylase and α-glucosidase synergistically to prevent hyperglycemia.

Variation in the metabolites and α-glucosidase inhibitory activity of Cosmos caudatus at different growth stages.

BACKGROUND: Cosmos caudatus is an annual plant known for its medicinal value in treating several health conditions, such as high blood pressure, arthritis, and diabetes mellitus. The α-glucosidase inhibitory activity and total phenolic content of the leaf aqueous ethanolic extracts of the plant at different growth stages (6, 8. 10, 12 and 14 weeks) were determined in an effort to ascertain the best time to harvest the plant for maximum medicinal quality with respect to its glucose-lowering effects. METHODS: The aqueous ethanolic leaf extracts of C. caudatus were characterized by NMR and LC-MS/MS. The total phenolic content and α-glucosidase inhibitory activity were evaluated by the Folin-Ciocalteu method and α-glucosidase inhibitory assay, respectively. The statistical significance of the results was evaluated using one-way ANOVA with Duncan's post hoc test, and correlation among the different activities was performed by Pearson's correlation test. NMR spectroscopy along with multivariate data analysis was used to identify the metabolites correlated with total phenolic content and α-glucosidase inhibitory activity of the C. caudatus leaf extracts. RESULTS: It was found that the α-glucosidase inhibitory activity and total phenolic content of the optimized ethanol:water (80:20) leaf extract of the plant increased significantly as the plant matured, reaching a maximum at the 10th week. The IC50 value for α-glucosidase inhibitory activity (39.18 µg mL- 1) at the 10th week showed greater potency than the positive standard, quercetin (110.50 µg mL- 1). Through an 1H NMR-based metabolomics approach, the 10-week-old samples were shown to be correlated with a high total phenolic content and α-glucosidase inhibitory activity. From the partial least squares biplot, rutin and flavonoid glycosides, consisting of quercetin 3-O-arabinofuranoside, quercetin 3-O-rhamnoside, quercetin 3-O-glucoside, and quercetin 3-O-xyloside, were identified as the major bioactive metabolites. The metabolites were identified by NMR spectroscopy (J-resolve, HSQC and HMBC experiments) and further supported by dereplication via LC-MS/MS. CONCLUSION: For high phytomedicinal quality, the 10th week is recommended as the best time to harvest C. caudatus leaves with respect to its glucose lowering potential.

Antioxidant activity, α-glucosidase inhibition and phytochemical profiling of Hyophorbe lagenicaulis leaf extracts.

BACKGROUND: Diabetes mellitus type II (DMT-2) is a widely spread metabolic disorder both in developed and developing countries. The role of oxidative stress is well established in DMT-2 pathogenesis. The synthetic drugs for DMT-2 are associated with serious side complications. Antioxidant and α-glucosidase inhibitory actions of phytochemicals from various plant species are considered as an alternative to synthetic drugs for DMT-2 management. The present study aimed to evaluate the antioxidant activity, α-glucosidase inhibitory potential and phytochemical profiling of Hyophorbe lagenicaulis. METHODS: The total phenolic and flavonoid contents, in vitro antioxidant activity (α, α-diphenyl-ß-picrylhydrazyl (DPPH) free radical scavenging and phosphomolybdenum method) and α-glucosidase inhibition of ultrasonicated hydroethanolic H. lagenicaulis leaf extracts were determined spectrophotometrically. The results of DPPH assay and α-glucosidase inhibition were reported in terms of IC50 value. The phytochemical profiling was accomplished by UHPLC-Q-TOF/MS/MS technique. RESULTS AND DISCUSSION: Findings leaped 60% ethanolic extract as rich fraction regarding total phenolic and flavonoid contents. The 60% ethanolic fraction was a promising source of natural antioxidants and α-glucosidase inhibitory agents as indicated by anti-radical and enzyme inibitory activities. Kaempferol, rutin, hesperetin 5-O-glucoside, kaempferol-coumaroyl-glucoside, luteolin 3-glucoside, Isorhamnetin-3-O-rutinoside, trimethoxyflavone derivatives and citric acid were identified by UHPLC-Q-TOF-MS/MS. These compounds were believed to be responsible for the strong antioxidant and enzyme inhibitory activity of plant extracts. The extensive metabolite profiling of H. lagenicaulis was carried out the first time as never reported previously. The H. lagenicaulis might be an appropriate choice to manage diabetes mellitus in an alternate way. The findings may be further exploited extensively for toxicity evaluation to proceed with functional food development having antidiabetic attributes.

Inhibition of UVB-induced pro-inflammatory cytokines and MMP expression by Zanthoxylum rhetsa bark extract and its active constituent hesperidin.

The antiphoto aging property of Zanthoxylum rhetsa obtained from Pangkor Island, Malaysia, was evaluated. Solvent fractions of different polarity obtained from the methanolic extract of the bark material were initially tested for anticollagenase and antielastase activities. The ethyl acetate fraction showed bioactivity against the protease enzymes. Hence, it was subjected to further purification via column chromatography, to yield a major constituent, hesperidin. Subsequently, the ethyl acetate fraction and hesperidin were tested for their effects against UVB-induced cytotoxicity and expressions of inflammatory cytokines (IL-6, IL-1ß, and TNF-α), NF-κB, and MMPs (MMP1, 3, and 9) in human dermal fibroblasts (HDF). Both fraction and pure compound prevented UVB-induced cytotoxicity in HDF cells, in a dose dependent manner. Moreover, the ethyl acetate fraction inhibited the increase of pro-inflammatory cytokines induced by UVB to a level similar to the control (without UV treatment). Additionally, the fraction significantly inhibited the expressions of NF-κB, MMP 1, MMP 3, and MMP 9 in HDF cells treated with UVB. Similar effects were observed with hesperidin. The results obtained suggested that the ethyl acetate fraction of Z. rhetsa and its bioactive constituent, hesperidin, have the potential to be used as active ingredients in sunscreen and antiphoto aging formulations.

Discriminative Analysis of Different Grades of Gaharu (Aquilaria malaccensis Lamk.) via ¹H-NMR-Based Metabolomics Using PLS-DA and Random Forests Classification Models.

Gaharu (agarwood, Aquilaria malaccensis Lamk.) is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The current study addresses the chemical differences and similarities between gaharu samples of different grades, obtained commercially, using ¹H-NMR-based metabolomics. Two classification models: partial least squares-discriminant analysis (PLS-DA) and Random Forests were developed to classify the gaharu samples on the basis of their chemical constituents. The gaharu samples could be reclassified into a 'high grade' group (samples A, B and D), characterized by high contents of kusunol, jinkohol, and 10-epi-γ-eudesmol; an 'intermediate grade' group (samples C, F and G), dominated by fatty acid and vanillic acid; and a 'low grade' group (sample E and H), which had higher contents of aquilarone derivatives and phenylethyl chromones. The results showed that ¹H- NMR-based metabolomics can be a potential method to grade the quality of gaharu samples on the basis of their chemical constituents.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.