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BackgroundPlants provide an alternative source to manage various human disorders due to diverse metabolites. Euphorbia dracunculoides of family Euphorbiaceae is used by local practitioners in rheumatism, epilepsy, edema, snake bite, warts and also possesses diuretic and purgative effects. The present study evaluated the antioxidant, anti-inflammatory and analgesic activities of various extracts of E. dracunculoides. Further, phytochemical constituents of the leading extracts were also investigated.MethodsDry powder of E. dracunculoides was extracted with n-hexane (EDH), acetone (EDA), ethanol (EDE), ethanol + water (1:1) (EDEW) and methanol (EDM) and screened for phytochemical classes, total phenolic (TPC) and flavonoid content (TFC). Antioxidant effects of the extracts were manifested by in vitro multidimensional assays. The anti-inflammatory and analgesic activities of the extracts were evaluated through carrageenan induced paw edema and hot plate test in rat. In addition, GC-MS analysis of EDH and HPLC-DAD analysis of EDEW was carried out to determine the presence of active constituents.ResultsQualitative analysis of various extracts of E. dracunculoides assured the existence of tannins and coumarins while presence of anthraquinones and anthocyanins was not traced in these extracts. Maximum quantity of TPC and TFC was recorded in EDEW followed by EDE. EDEW and EDE showed significant antioxidant activities with therapeutic potential against hydroxyl and phosphomolybdate radicals, β-carotene bleaching assay and in reducing of iron while moderate to low scavenging abilities were recorded for DPPH, nitric oxide and for iron chelation. During anti-inflammatory activity after 4 h of drug administration the 300 mg/kg body weight dose of EDH (68.660 ± 10.502 %) and EDE (51.384 ± 8.623 %) exhibited strong anti-inflammatory activity and reduced the carrageenan-induced paw edema in rat as compared to standard drug diclofenac sodium (78.823 ± 6.395 %). Treatment of rats with EDH (70.206 ± 5.445 %) and EDE (56.508 ± 6.363 %) after 90 min showed significant increase in percent latency time in hot plate test as compared to morphine (63.632 ± 5.449 %) treatment in rat. GC-MS analysis of EDH indicated the presence of 30 compounds predominantly of steroids and terpenoids. HPLC-DAD analysis against known standards established the presence of rutin, catechin, caffeic acid and myricetin in EDEW.ConclusionOur results suggest that presence of various polyphenolics, terpenoids and steroids render E. dracunculoides with therapeutic potential for oxidative stress and inflammation related disorders.

Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria Streptomyces sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain Streptomyces sp. SH-1312 with addition of mix metals (Co2+ + Zn2+) ions at 0.5 mM in Gause’s medium. Under these conditions, the stress metabolite anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC50 value of 19.65 ± 5.7 µg/mL in DPPH, IC50 of 15.49 ± 4.8 against NO free radicals, the IC50 value of 19.65 ± 5.22 µg/mL against scavenging ability, and IC50 value of 19.38 ± 7.11 µg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC50 values of 35.81 ± 4.2 µg/mL after 24 h, 23.29 ± 3.8 µg/mL at 48 h, and 16.25 ± 6.5 µg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.

BackgroundIpomoea batatas L. Lam. is a functional food and belongs to family Convolvulaceae. It is used as an antiinflammatory, aphrodisiac, antiasthmatic, anticonvalescent, antitumor, antanemic and antidiabetic agent by local communities. This study has been planned to evaluate its antiinflammatory and antiarthritic potentials.MethodsDry powder of I. batatas tuber and roots were extracted with ethyl acetate (IPT-EA, IPR-EA) and methanol (IPT-M, IPR-M), respectively. These extracts were tested for total phenolic and flavonoid contents (TPC and TFC), HPLC finger printing, multidimensional in vitro and in vivo antioxidant potential and albumin denaturation inhibition. Carrageenan-induced paw edema, croton oil-induced ear and anal edema inhibition and Complete Freund’s Adjuvant (CFA)-induced antiarthritic assays were executed at a dose of 300 mg/kg body weight on Sprague-Dawley rats. Serum levels of interleukins IL-1β and IL-6 and nitric oxide (NO) were assessed to measure the inhibition of inflammation.ResultsMaximal TPC (319.81 ± 14.20 μg GAE/mg dry extract) and TFC (208.77 ± 9.09 μg QE/mg DE) were estimated in IPR-EA extract. IPT-EA and IPR-EA yielded the maximum amounts of rutin (7.3 ± 1.12 and 4.5 ± 0.55), caffeic acid (1.60 ± 0.25 and 2.17 ± 0.26) and myricetin (2.7 ± 0.14 and 1.01 ± 0.08 μg/mg DE), respectively in HPLC-DAD analysis. All extracts showed dose dependent response in in vitro antioxidant assays. Best inhibition (76.92 ± 3.07%) of albumin denaturation was shown by IPT-EA in comparison to ibuprofen (79.48 ± 4.71%). IPR-EA exhibited highest edema inhibition in models of carrageenan-induced paw edema (79.11 ± 5.47%) and croton oil-induced ear and anal edema (72.01 ± 7.80% and 70.80 ± 4.94%, respectively). Significant inhibition of CFA-induced arthritic edema and arthritic score were observed by IPR-EA as compared to ibuprofen. Suppression of pro-inflammatory cytokines (IL-1β, IL-6) and NO levels was shown by IPR-EA and IPT-EA, respectively.ConclusionThese results depict that richness of polyphenols and phytoconstituents in I. batatas ameliorates oxidative stress and inflammation of acute and chronic nature. Dose dependent antioxidant potential and inhibition of inflammatory edema, pro-inflammatory cytokines and hematological, biochemical and histological changes prove I. batatas therapeutic potential as an antiinflammatory and antiarthritic agent.Graphical abstract Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2279-5) contains supplementary material, which is available to authorized users.

BackgroundDifferent parts of Fraxinus xanthoxyloides Wall. (Oleaceae) are used traditionally in the treatment of internal wounds, bone fracture, pain, jaundice, malaria and in pneumonia. These ailments involve protective and essential mechanisms of the organism in response to infection, injury and trauma. However, prolonged inflammation may lead to inflammatory disorders. The present investigation was carried to evaluate the crude methanol extract of F. xanthoxyloides leaves and its fractions for their anti-inflammatory and analgesic effects.MethodsMethanol extract of F. xanthoxyloides leaves was fractionated through liquid-liquid partition on escalating polarity of solvents. Acetic acid and thermal responses were used to evaluate the analgesic effects of extract/fractions in rat. Anti-inflammatory effects were monitored through in vitro; TNF-α activated NFkB in 293/NFkB-Luc HEK cells and LPS-activated nitric oxide (NO) assay in RAW 264.7 cells. For in vivo studies carrageenan induced paw edema model was used in rat. Both in vitro and in vivo studies have indicated that chloroform fraction exhibited superior anti-inflammatory effects to other extract/fractions and therefore, was used in air pouch model in rat to estimate the inhibition in leukocyte migration and synthesis of inflammatory mediators. In addition, phytochemical investigation of crude extract was carried out by GC-MS analysis.ResultsGC-MS studies of crude extract revealed the presence of various classes of which terpenoids (26.61 %), lactam (16.47 %), esters (15.81 %), phenols (8.37 %), and steroid (6.91 %) constituted the major categories. Among the extracts chloroform fraction (200 mg/kg bw) significantly (P <0.001) increased the percent latency time (76.13 ± 4.49 %) in hot plate test after 120 min and decreased (P <0.001) the count of writhes (77.23 ± 5.64 %) as compared to other extracts. The in vitro studies indicated that chloroform fraction at 15 μg/ml more effectively inhibited the TNF-α induced synthesis of NFkB (85.0 ± 8.12 %, IC50 = 5.98 μg/ml) and LPS-instigated nitric oxide (78.23 ± 2.39 %, IC50 = 6.59 μg/ml) synthesis. Although all the extract/fractions showed a dose dependent increase in inhibition of edema formation however, chloroform fraction (4th h = 77.64 ± 3.04 %) at 200 mg/kg bw exhibited relatively higher (P <0.001) anti-inflammatory activity in carrageenan-induced paw edema in rat. Moreover, chloroform fraction had the ability to decrease (P <0.001) the influx of leukocytes and the concentration of inflammatory mediators; TNF-α, NO, IL-6 and PGE2 in air pouch exudate.ConclusionThe study demonstrates the therapeutic potential of F. xanthoxyloides leaves against the inflammatory disorders suggesting the presence of active constituents in chloroform fraction.

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BackgroundEvaluation of Euphorbia dracunculoides of family Euphorbiaceae during previous studies had established the in vitro antioxidant and in vivo anti-inflammatory activities. The plant is used by the local communities of Pakistan for various disorders including rheumatism and edema. In this investigation we have evaluated the hepatoprotective effects against CCl4 induced toxicity in rat.MethodsDry powder of the aerial parts of E. dracunculoides was extracted with 95% methanol to get the extract (EDME). To investigate the hepatoprotective effects of EDME the Sprague-Dawley male rats were divided in to 8 groups with 6 rats in each. Group I and II were the normal and vehicle treated while the Groups III-VI were injected intraperitoneally with 1 ml of CCl4 (30% in olive oil). Rats of Group IV were orally administered with silymarin (50 mg/kg) while the Group V and VI with 200 mg/kg and 400 mg/kg of EDME, respectively. Animals of Group VII (200 mg/kg) and VIII (400 mg/kg) were treated with EDME alone. The treatments were given thrice a week for 4 weeks. Effects of EDME were evaluated for the protective effects against oxidative stress and genotoxicity induced with CCl4 in liver of rat.ResultsAnalysis of serum indicated significant (p < 0.05) rise in the level of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and globulin whereas decrease was recorded for the total protein and albumin in CCl4 treated rats. In liver tissues the activity level of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione (GSH) was decreased while the level of lipid peroxides; thiobarbituric acid reactant substances (TBARS), nitrite and hydrogen peroxide increased in CCl4 treated rats as compared to the control group. Histopathological injuries and DNA damages were recorded in liver of rat with CCl4 treatment. However, co-administration of EDME, dose dependently, ameliorated the CCl4-induced hepatic toxicity in these parameters.ConclusionsThese results suggested that the phyto-constituents of EDME were able to ameliorate the oxidative stress induced with CCl4 and can be a useful therapeutic agent for oxidative stress related disorders.