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The aim of the study was to investigate the relationship between flavonoids in Abrus precatorius leaves (APL) and their hypoglycaemic effects, which have not been studied before. An efficient purification process, transcriptomics and network pharmacology analysis were applied for the first time. High-performance liquid chromatography (HPLC) was used to determine the content of total flavonoids. The results showed that D101 resin was most suitable for purification of flavonoids of APL, which could increase its purity from 25.2% to 85.2% and achieve a recovery rate of 86.9%. The analysis of transcriptomics and network pharmacology revealed that flavonoids of APL could play a hypoglycaemic role by regulating 31 targets through AGE-RAGE and other signal pathways. Flavonoids of APL could exert hydroglycaemic effects by inhibiting AGEs, α-glucosidase and DPPH. This study provides a solid basis for hypoglycaemic product development and in-depth research of flavonoids in APL.

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Objective: Hydroxytyrosol (HT) is a polyphenol with a wide range of biological activities. Excessive drinking can lead to oxidative stress and inflammation in the liver, which usually develop into alcohol liver disease (ALD). At present, there is no specific drug to treat ALD. In this paper, the protection effect of HT on ALD and the underline mechanism were studied.Methods: HepG2 cells were exposed to ethanol in vitro and C57BL/6J mice were fed with a Lieber-DeCarli ethanol liquid diet in vivo.Results: triglyceride (TG) level in serum and the expression of fatty acid synthase (FASN) were reduced significantly by the treatment with HT The acetaldehyde dehydrogenase (ALDH) activity was increased, the serum level of malondialdehyde (MDA) was decreased, catalase (CAT) and glutathione (GSH) were increased, suggesting that HT may reduce its oxidative damage to the body by promoting alcohol metabolism. Furthermore, according to the mRNA levels of tnf-α, il-6 and il-1ß, HT inhibited ethanol-induced inflammation significantly. The anti-inflammatory mechanism of HT may be related to suppress the STAT3/iNOS pathway.Dissussion: Our study showed that HT could ameliorate ethanol-induced hepatic steatosis, oxidative stress and inflammation and provide a new candidate for the prevention and treatment of ALD.

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The layer-by-layer application of biopolymeric coatings to mandarin fruits as a postharvest treatment to improve fruit coating efficacy has been reported. A single 1 % (w/v) chitosan application was evaluated, and polyelectrolyte complexes such as 1.5 % (w/v) alginate/chitosan, 1 % (w/v) hydroxypropyl methylcellulose/chitosan, and 0.2 % (w/v) locust bean gum/chitosan were applied to mandarin fruits. The quality of coated mandarin fruits was observed at temperatures: 20 ± 2 °C (up to 10 days) and 5 °C (up to 28 days). Changes in the fruit metabolism were observed by evaluating bioactive compounds (polyphenolic compounds and flavonoids), antioxidant activity, and organic acids during the preservation of mandarin fruits. All of the tested combinations of layer-by-layer coatings significantly impacted the quality of mandarin fruits throughout storage, both at room temperature and cold storage, respectively. The overall best performance was observed for a layer-by-layer hydroxypropyl methylcellulose/chitosan coating in terms of visual aspects, bioactive compounds, antioxidant activity, and organic acids content.

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Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

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The present study examined the phytochemical composition, antioxidant, antimicrobial properties, and molecular docking of different solvents extracts (methanol and water) of two medicinal plants, namely, Capparis spinosa L (CS) and Rumex nervosus (RN). Phytochemical analysis showed that total phenol, flavonoids, alkaloids, and vitamin C were significantly (P ≤ 0.05) higher in the methanolic extract of both plants than in other solvents. However, tannin content was significantly (P ≤ 0.05) high in the water extract for both plants. Chloroform and acetone extracts were significantly lower in phytochemicals than other solvents, therefore excluded in this study. GC-MS analysis showed one dominant compound in CS (isopropyl isothiocyanate) and two in RN (pyrogallol and palmitic acid). The antioxidant methods applied (DPPH, ABTS, ß-Carotene/linoleic acid assay, and reducing the power) showed that the methanolic extract of CS exerted higher activity in methanolic extract but lower than that of BHA standard. The methanolic extract of both plants inhibited the bacterial pathogens when a minimum inhibitory concentration (MIC) method was applied, compared to water extract with RN-methanolic extract had a lower inhibition concentration than CS-methanolic extract. The molecular interactions study revealed that the palmitic acid and pyrogallol interacted with the receptors' active site. This work concluded that CS and RN showed a remarkable antioxidant and antibacterial effect with the high antimicrobial activity of RN extract.

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Multitude of diseases and side effects from conventional drugs have surged the use of herbal remedies. Thus, the current study aimed to appraise various pharmacological attributes of Artemisia brevifolia Wall. ex DC. Extracts prepared by successive solvent extraction were subjected to phytochemical and multimode antioxidant assays. Various polyphenolics and artemisinin derivatives were detected and quantified using RP-HPLC analysis. Compounds present in methanol (M) and distilled water (DW) extracts were identified using high resolution mass spectrometry (HRMS). Extracts were pharmacologically evaluated for their antibacterial, antifungal, antimalarial, antileishmanial and antidiabetic potentials. Moreover, cytotoxicity against Artemiasalina, human cancer cell lines and isolated lymphocytes was assessed. Genotoxicity was evaluated using comet, micronucleus and chromosomal aberration assays. Lastly, anti-inflammatory potential was determined through a series of in vitro and in vivo assays using BALB/c mice. Maximum extract recovery (5.95% w/w) was obtained by DW extract. Highest phenolics and flavonoids content, total antioxidant capacity, total reduction potential, percentfree radical scavenging, ß-carotene scavenging and iron chelating activities were exhibited by M extract. RP-HPLC analysis revealed significant amounts of various polyphenolic compounds (vanillic acid, syringic acid, emodin and luteolin), artemisinin, dihydro artemisinin, artesunate and artemether in ethyl acetate (EA) extract. Total 40 compounds were detected through HRMS. A noteworthy antimicrobial activity (MIC 22.22 µg/ml) was exhibited by EA extract against A. fumigatus and several bacterial strains. Maximum antimalarial, antileishmanial, brine shrimp lethality and cytotoxic potential against cancer cells was manifested by EA extract. None of the extracts exhibited genotoxicity and toxicity against isolated lymphocytes. Highest α-amylase and α-glucosidase inhibition capacities were demonstrated by DW extract. Various in-vivo anti-inflammatory models revealed significant (p < 0.05) anti-inflammatory potential of M and DW extracts. In conclusion, present findings divulged theremarkable pharmacological potential of A. brevifolia and endorse its richness in artemisinin.

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Background: In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods: The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H2O2, and the keratinocyte cells were treated with SYR (0-200 µg/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results: SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H2O2-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC50 value of 10.77 and 10.35 µg/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H2O2-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion: SYR showed antioxidant activity and up-regulated autophagy activity in H2O2-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

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Objective: To determine antioxidant potentials of Allium sativum and Persea americana seeds extracts and three formulation-based extracts in vitro, and to evaluate the effects of the best formulation on oxidative stress and dyslipidemia on rats fed with high fat and high sucrose diet (HFHSD). Methods: Aqueous extracts of Allium sativum, Persia. americana and three formulations were mixed at various portions (A. s/P. a; w/w): F (1:1), F (3: 1), and F(1:3). They were then tested for their antioxidant potentials in vitro using FRAP, DPPH and NO radicals to identify the best formulation. Four hundred (400) mg/kg b.w. of formulation F(1:1) were administered once daily for 21 days to rats previously fed with HFHSD for 8 weeks. Standard diet, vitamin E, and Atorvastatin were used as controls. After 21 days, body weight, blood glucose, lipid markers, activities of transaminases and markers of the antioxidant systems were assessed. Results: The Formulation F(1:1) showed the best in vitro activity with IC50 values of 6.5 and 2.23 mg/mL respectively for FRAP and DPPH- radical scavenging capacity. HFHSD caused a depletion of antioxidants associated with an increase of pro-oxidants and all the lipid markers except HDL-c Treatment with F(1:1) significantly increased TAC, SOD, and catalase activities, while MDA, protein carbonyls, and NO levels decreased (p < 0.05). Formulation F(1:1) decreased triglycerides (119.88 ± 4.25 mg/dL) and LDL-c (3.78 ± 0.66 mg/dL) levels and significantly increased the HDL-c level: (108.07 ± 6.29 mg/mL). Furthermore, Formulation F(1:1) significantly caused weight loss (2.31%), reduced blood glucose levels (27.38%) and ALT activity. Conclusion: The formulation F(1:1) could be a good candidate for the prevention and treatment of oxidative stress, dyslipidemia and features of metabolic syndrome.

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Bacterial exopolysaccharides are high molecular weight polysaccharides that are secreted by a wide range of bacteria, with diverse structures and easy preparation. Fucose, fucose-containing oligosaccharides (FCOs), and fucose-containing polysaccharides (FCPs) have important applications in the food and medicine fields, including applications in products for removing Helicobacter pylori and infant formula powder. Fucose-containing bacterial exopolysaccharide (FcEPS) is a prospective source of fucose, FCOs, and FCPs. This review systematically summarizes the common sources and applications of FCPs and FCOs and the bacterial strains capable of producing FcEPS reported in recent years. The repeated-unit structures, synthesis pathways, and factors affecting the production of FcEPS are reviewed, as well as the degradation methods of FcEPS for preparing FCOs. Finally, the bioactivities of FcEPS, including anti-oxidant, prebiotic, anti-cancer, anti-inflammatory, anti-viral, and anti-microbial activities, are discussed and may serve as a reference strategy for further applications of FcEPS in the functional food and medicine industries.

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We aimed to explore the effects of the 60Co-γ irradiated ginseng adventitious root (GAR) with different radiation doses on the hypoglycemic effects of its extract (GARSE) through in vivo and in vitro experiments. The total saponin of GARSE was increased by 4.50% after 5 kGy irradiation, and the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability was enhanced by 5.10%. At 50 µg/mL, GARSE irradiated by 5 kGy displayed superior protective effects on human glomerular mesangial cells (HMCs) with high glucose damage. After feeding type 1 diabetes mellitus (T1DM) mice with GARSE irradiated by 5 kGy at 500 mg/kg·BW for 4 weeks, the glucose values was decreased by 16.0% compared with the unirradiated. The Keap1/Nrf2/HO-1 pathway was activated and the oxidative stress was attenuated, which further alleviated T1DM.

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Background and aim: Secretory diarrhea is the most common type of diarrhea. This study aimed at exploring the possible mechanism of antisecretory action of Annona senegalensis stem bark and to identify the bioactive compounds. Experimental procedure: The ability of three crude extract; aqueous, dichloromethane and hexane stem bark extracts to inhibit castor oil-induced stooling in albino rats were assessed. Bioactivity guided fractionation of the most active extract was done using solvent-solvent partitioning (with hexane, dichloromethane, ethylacetate) and column chromatography. In vitro antioxidant activity of the most active sub-fraction was done using standard methods. The most active sub-fraction (25 mg/kg b. wt.) was administered to castor oil-induced diarrheal rats. Diarrheal rats small intestinal malondialdehyde concentration, antioxidant enzyme, cyclooxygenase II and Na+- K+ ATPase activities were determined using standard procedures. GC-MS analysis was done to identify the chemical compounds in the sub-fraction. Result and conclusion: Aqueous extract significantly decreased the number of wet stools. Sub-fraction 1 of ethylacetate fraction of aqueous stem bark extract (EFAS1) showed the highest stool inhibition. The H2O2 scavenging activity of EFAS1 was significantly greater than ascorbic acid. The sub-fraction significantly increased (p < 0.05) the activity of catalase and Na+- K+ ATPase activities but significantly decreased the concentration of malondialdehyde and cyclooxygenase II activity. GC-MS analysis revealed that EFAS1 is rich in catechol, n-hexadecanoic acid and ethyl-5,8,11,14,17-icosapentanoate. The sub-fraction exerts its antisecretory activity by its antioxidative, inhibition of prostaglandin synthesis and stimulation of Na+- K+ ATPase properties due to the presence of catechol, n-hexedecanoic acid and ethyl-5,8,11,14,17-icosapentanoate.

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Porphyromonas gingivalis, the cause of periodontitis, is also linked to many systemic disorders due to its citrullination capability from a unique peptidyl arginine deiminase (PPAD). Protein citrullination is able to trigger an autoimmune response, increasing the severity of rheumatoid arthritis. The main objective of this study is to evaluate the inhibitory activity of Cratoxylym cochinchinense leaves extract towards the PPAD in vitro and in silico. Methanolic extract of Cratoxylum cochinchinense (CCM) was tested for total phenolic and flavonoid contents along with antioxidative assays. Inhibition of PPAD activities was conducted thereafter using recombinant PPAD in cell lysate. Phytocompounds postulated present in the CCM such as mangiferin, vismiaquinone A, δ-tocotrienol and α-tocotrienol and canophyllol were used as ligands in a simulated docking study against PPAD. Results obtained indicated high antioxidant potential in CCM while recording abundant phenolic (129.0 ± 2.5495 mg GA/g crude extract) and flavonoid (159.0 ± 2.1529 mg QE/g crude extract) contents. A dose-dependent inhibition of PPAD was observed when CCM was evaluated at various concentrations. CCM at 1 mg/mL exhibited citrulline concentration of 24.37 ± 3.25 mM which was 5 times lower than the negative control (114.23 ± 3.31 mM). Molecular docking simulation revealed that mangiferin and vismiaquinone A engaged in H-bonding and pi-pi interactions with important active site residues (Asp130, Arg152, Arg154 and Trp127) of PPAD and could be the potential phytochemicals that accounted for the inhibitory activities observed in the methanolic leaves extract. As such, CCM could be further explored for its therapeutic properties not only for periodontitis, but also for other systemic diseases like rheumatoid arthritis.

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Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

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The purpose of this work was to investigate the protective effect of five essential oils (EOs); Rosmarinus officinalis, Thymus vulgaris, Origanum compactum Benth., Eucalyptus globulus Labill. and Ocimum basilicum L.; against oxidative stress induced by hydrogen peroxide in Saccharomyces cerevisiae. The chemical composition of the EOs was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The in vitro antioxidant activity was evaluated and the protective effect of EOs was investigated. Yeast cells were pretreated with different concentrations of EOs (6.25-25 µg/ml) for an hour then incubated with H2O2 (2 mM) for an additional hour. Cell viability, antioxidants (Catalase, Superoxide dismutase and Glutathione reductase) and metabolic (Succinate dehydrogenase) enzymes, as well as the level of lipid peroxidation (LPO) and protein carbonyl content (PCO) were evaluated. The chemical composition of EOs has shown the difference qualitatively and quantitatively. Indeed, O. compactum mainly contained Carvacrol, O. basilicum was mainly composed of Linalool, T. vulgaris was rich in thymol, R. officinalis had high α-Pinene amount and for E. globulus, eucalyptol was the major compound. The EOs of basil, oregano and thyme were found to possess the highest amount of total phenolic compounds. Moreover, they have shown the best protective effect on yeast cells against oxidative stress induced by H2O2. In addition, in a dose dependent manner of EOs in yeast medium, treated cells had lower levels of LPO, lower antioxidant and metabolic enzymes activity than cells exposed to H2O2 only. The cell viability was also improved. It seems that the studied EOs are efficient natural antioxidants, which can be exploited to protect against damages and serious diseases related to oxidative stress.

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In the present study, 30 potential germplasm of oat (Avena sativa L.) were subjected to proximate, elemental, and HPLC analysis to provide a scientific basis to genetic diversity present among them. The extracts of the selected germplasms were also evaluated for their antioxidant potentials through DPPH and ABTS assays. Proximate analysis showed protein contents to be in the range 8.35-17.72% with the highest protein contents in the accession line 22,365 (17.72 ± 0.38%). The genotype-725 showed the highest carbohydrate, and dry matter (53.35 ± 0.01 and 93.50 ± 0.07% respectively) contents whereas, the germplasm-830 contained the highest fat (7.88 ± 0.12%) contents while the highest moisture contents were there in germplasm-22348 (11.95 ± 0.06%). The crude fiber contents (19.67 ± 0.19%) were found high in germplasm-832. The mentioned contents were also correlated to each other where a negative (-0.431*) correlation was noted for crude protein and carbohydrate while ash content to crude protein has a positive (0.38*) correlation. A positive and a negative correlation were there in Crude fats/crude protein (0.30*) and crude fats/moisture contents (-0.39*) respectively. Principal component analysis showed an Eigenvalue of 0.76 with a total variation of 85.01% when applied to proximate components. Based on cluster analysis to proximate composition all the oat germplasms were divided into 5 sub-clusters, where accession numbers 769 and 817 were found to be the most diverse genotypes. The elemental analysis confirmed the presence of magnesium (2.89-7.62 mg/L), sodium (3.71-8.03 mg/L), manganese (0.93-3.71 mg/L), copper (0.35-3.36 mg/L), iron (2.15-6.82 mg/L), zinc (1.30-3.37 mg/L), chromium (0.37-3.34 mg/L), and potassium (50.70-59.60 mg/L) in the selected germplasms. Principal component analysis for elemental composition showed the total variation of 73.75% with the Eigenvalue of 0.97. Cluster analysis on an elemental basis divided all the oat germplasms into 7 sub-clusters where accession numbers 769 and 22,350 were found to be the most diverse germplasm. Phytochemical analysis performed through HPLC resulted in the identification of nine possible compounds (malic acid, epigallocatechin gallate, quercetin, morin, ellagic acid, catechin hydrate, rutin, pyrogallol, and mandelic acid) in various germplasm of oat. A concentration-dependent antioxidant response was recorded when extracts were tested as an inhibitor of DPPH and ABTS free radicals. The results revealed that oat grains are a good source of nutrients, minerals, and phytochemicals that can be used as nutraceuticals and as food. The genetic differences revealed that this plant can be grown under varied environmental conditions.

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This study aimed to identify compounds in 12 minor Zingiberaceae spices grown in Indonesia linked with in vitro α-glucosidase inhibitor and antioxidant (DPPH, FRAP, CUPRAC) activities using SPME-GC/MS volatilomics. The results illustrated that Zingiber aromaticum Val., Alpinia malaccensis (Burm.f.) Roscoe, Amomum compactum Sol. ex Maton, and Zingiber purpureum Roscoe had the highest α-glucosidase inhibitor and DPPH, FRAP, CUPRAC antioxidant activities, respectively. Also, the total phenolic content positively influenced DPPH, FRAP, and CUPRAC antioxidant activities. The strongest positive correlation with α-glucosidase inhibitor and DPPH antioxidant activities was found in eucalyptol; whereas o-cymene and terpinen-4-ol had the strongest correlations with FRAP and CUPRAC antioxidants, respectively. Furthermore, the molecular docking analysis revealed that all compounds with a strong correlation with α-glucosidase inhibitor activity (based on their OPLS VIP score) had binding energies (-5.06 - -6.26 kcal/mol) close to Acarbose (-10.11 kcal/mol). Thus, this study provided vital information on the volatile compounds in underutilized spices associated with their health beneficial properties.

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The paracetamol-induced injuries of liver and kidneys in animals are mostly used to screen out the hepato and nephroprotective effect of extract or other therapeutic agents. In the present study total phenolic and flavonoid contents, in vitro antioxidant, and in vivo hepato/nephroprotective (on paracetamol-induced intoxication in experimental rabbits) potentials of the Daphne mucronata leaves methanolic extract were determined. For the identification of possible phytochemicals, HPLC (high performance liquid chromatography) analysis was carried out and a total of eight phenolic compounds; malic acid, gallic acid, chlorogenic acid, epigallocatechin gallate, quercetin, morin, ellagic acid, and rutin were identified. D. mucronata extract at doses of 250 and 500 mg/kg body weight were given for eight days to paracetamol intoxicated rabbits and the observed results were compared with standard Silymarin. The level of liver enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum triglyceride, serum cholesterol, serum bilirubin, and kidneys biomarkers like serum urea, uric acid, and creatinine, as well as lipid peroxidation malondialdehyde contents were increased while the antioxidant enzymes like reduced glutathione and total antioxidant capacity were decreased. Furthermore, histopathological analysis of the liver and kidney tissues of control and treated groups also confirmed the hepatoprotective and nephroprotective effect of the D. mucronata which was most probably due to its high antioxidant phenolic and flavonoid phytoconstituents.

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Eleutherine plicata has been shown to be a promising medicinal plant, and its activity has been associated with naphthoquinones. The present study aimed at evaluating the cytotoxicity, genotoxicity, and oral toxicity of the ethanol extract (EEEp), dichloromethane fraction (FDMEp) of E. plicata, and isoeleutherin. For the cytotoxicity evaluation, the viability test (MTT) was used. Genotoxicity was accessed through the Comet assay (alkaline version), acute and subacute oral toxicities were also evaluated. The antioxidant capacity of the samples in the wells where the cells were treated with E. plicata was evaluated. Furthermore, the participation of caspase-8 in the possible mechanism of action of isoeleutherin, eleutherin, and eleutherol was also investigated through a docking study. FDMEp and isoeleutherin were cytotoxic, with higher rates of DNA fragmentation observed for FDMEp and isoeleutherin, and all samples displayed higher antioxidant potential than the control. In the acute oral toxicity test, EEEp, FDMEp, and isoeleutherin did not cause significant clinical changes. In the subacute toxicity assay, EEEp and FDMEp also did not cause clinical, hematological, or biochemical changes. The three compounds bound similarly to caspase-8. Despite the results of cytotoxicity, in vitro studies demonstrated that the use of EEEp appears to be safe and cell death may involve its binding to caspase-8.

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Anti-tumour efficacy of doxorubicin is hindered by the cumulative dose-dependent cardiotoxicity induced by reactive oxygen species during its metabolism. As Cinnamomum zeylanicum has proven antioxidant potential, objective of this study was to investigate the cardioprotective activity of Cinnamomum bark extract against doxorubicin induced cardiotoxicity in Wistar rats. Physicochemical and phytochemical analysis was carried out and dose response effect and the cardioprotective activity of Cinnamomum were determined in vivo. 180 mg/kg dexrazoxane was used as the positive control. Plant extracts were free of heavy metals and toxic phytoconstituents. In vivo study carried out in Wistar rats revealed a significant increase (p < 0.05) in cardiac troponin I, NT-pro brain natriuretic peptide, AST and LDH concentrations in the doxorubicin control group (18 mg/kg) compared to the normal control. Rats pre-treated with the optimum dosage of Cinnmamomum (2.0 g/kg) showed a significant reduction (p < 0.05) in all above parameters compared to the doxorubicin control. A significant reduction was observed in the total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activity while the lipid peroxidation and myeloperoxidase activity were significantly increased in the doxorubicin control group compared to the normal control (p < 0.05). Pre-treatment with Cinnamomum bark showed a significant decrease in lipid peroxidation, myeloperoxidase activity and significant increase in rest of the parameters compared to the doxorubicin control (p < 0.05). Histopathological analysis revealed a preserved appearance of the myocardium and lesser degree of cellular changes of necrosis in rats pre-treated with Cinnamomum extract. In conclusion, Cinnamomum bark extract has the potential to significantly reduce doxorubicin induced oxidative stress and inflammation in Wistar rats.

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Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4'-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4'-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles.