Targeting gut barrier dysfunction with phytotherapies: Effective strategy against chronic diseases.

The intestinal epithelial layer serves as a physical and functional barrier between the microbe-rich lumen and immunologically active submucosa; it prevents systemic translocation of microbial pyrogenic products (e.g. endotoxin) that elicits immune activation upon translocation to the systemic circulation. Loss of barrier function has been associated with chronic 'low-grade' systemic inflammation which underlies pathogenesis of numerous no-communicable chronic inflammatory disease. Thus, targeting gut barrier dysfunction is an effective strategy for the prevention and/or treatment of chronic disease. This review intends to emphasize on the beneficial effects of herbal formulations, phytochemicals and traditional phytomedicines in attenuating intestinal barrier dysfunction. It also aims to provide a comprehensive understanding of intestinal-level events leading to a 'leaky-gut' and systemic complications mediated by endotoxemia. Additionally, a variety of detectable markers and diagnostic criteria utilized to evaluate barrier improving capacities of experimental therapeutics has been discussed. Collectively, this review provides rationale for targeting gut barrier dysfunction by phytotherapies for treating chronic diseases that are associated with endotoxemia-induced systemic inflammation.

Poria ameliorates the side effects of rhubarb in pair treatment.

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P<0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P<0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

Albizia Adianthifolia: Botany, Medicinal Uses, Phytochemistry, and Pharmacological Properties.

The bark, leaves, and roots of Albizia adianthifolia are highly sought after in tropical Africa as herbal medicines. Therefore, the aim of this study was to review the botany, medicinal uses, phytochemistry, and pharmacological properties of A. adianthifolia so as to provide baseline data required for evaluating the therapeutic potential of the species. Information on the botanical profile, medicinal uses, phytochemistry, and pharmacological properties of A. adianthifolia was undertaken using databases such as ScienceDirect, SciFinder, Pubmed, Google Scholar, Medline, SCOPUS, EThOS, ProQuest, OATD, and Open-thesis. Preelectronic literature search of conference papers, scientific articles, books, book chapters, dissertations, and theses was carried out at the University library. Literature search revealed that A. adianthifolia is used as purgative and herbal medicine for diabetes, eye problems, gastrointestinal problems, haemorrhoids, headache, neurodegenerative disorders, reproductive problems in women, respiratory problems, wounds and pain, skin diseases, sexually transmitted infections, and ethnoveterinary medicine. Phytochemical compounds identified from the species include apocarotenoids, chalcone, dipeptide, elliptosides, essential oils, fatty acids, flavonoids, histamine, imidazolyl carboxylic acid, prosapogenins, steroids, triterpene saponins, and triterpenoids. Pharmacological studies revealed that A. adianthifolia extracts and compounds have acetylcholinesterase enzyme inhibitory, anthelmintic, antiamoebic, antibacterial, antimycobacterial, anti-sexually transmitted infections, antifungal, anti-inflammatory, antioxidant, anxiolytic, and antidepressant, cognitive-enhancing, haemolytic, hypoglycemic and antihyperglycemic, immunomodulatory, and cytotoxicity activities. Detailed studies on the pharmacokinetics, in vivo, and clinical research involving compounds isolated from A. adianthifolia and extracts of the species are required.

Gastroprotective and antielastase effects of protein inhibitors from Erythrina velutina seeds in an experimental ulcer model.

Trypsin and chymotrypsin inhibitors from Erythrina velutina seeds have been previously isolated by our group. In previous studies using a sepsis model, we demonstrated the antitumor and anti-inflammatory action of these compounds. This study aimed to evaluate the gastroprotective and antielastase effects of protein inhibitors from E. velutina seeds in an experimental stress-induced ulcer model. Two protein isolates from E. velutina seeds, with antitrypsin (PIAT) and antichymotrypsin (PIAQ) activities, were tested. Both protein isolates showed a high affinity and inhibitory effect against human neutrophil elastase, with 84% and 85% inhibition, respectively. Gastric ulcer was induced using ethanol (99%) in 6 groups of animals (female Wistar rats, n = 6). Before ulcer induction, these animals were treated for 5 days with one of the following: (1) PIAT (0.2 mg·kg-1), (2) PIAT (0.4 mg·kg-1), (3) PIAQ (0.035 mg·kg-1), (4) ranitidine hydrochloride (50 mg·kg-1), (5) saline solution (0.9%), or (6) no intervention (sham). Both PIAT and PIAQ protected gastric mucosa, preventing hemorrhagic lesions, edema, and mucus loss. No histologic toxic effects of PIAT or PIAQ were seen in liver and pancreatic cells. Our results show that protein isolates from E. velutina seeds have potential gastroprotective effects, placing these compounds as natural candidates for gastric ulcer prevention.

Anti-inflammatory and gastroprotective potential of leaf essential oil of Cinnamomum glanduliferum in ethanol-induced rat experimental gastritis.

CONTEXT: Nothing could be found in the literature concerning Cinnamomum glanduliferum (Wall) Meissn (Lauraceae) bark (CG) in Egypt. OBJECTIVE: To investigate CG volatile oil chemically and its anti-inflammatory and gastroprotective effects. MATERIALS AND METHODS: Essential oils were investigated by GC-MS. Leaves oil was assessed at doses of 250, 500 and 1000 mg/kg for its anti-inflammatory effect against carrageenan-induced rat oedema model. Serum inflammation markers were measured. The gastro-protective effect of the same doses of the volatile oil was also tested in ethanol-induced non-ulcerative gastritis model in rats. Stomach oxidative stress markers were examined following 1 h after intragastric ethanol administration. RESULTS: Twenty-five and 20 compounds were identified from leaf and branch oils, respectively (98.85 and 99.13%). The major ones were: eucalyptol (59.44%; 55.74%), sabinene (14.99%; 7.12%), α-terpineol (6.44%; 9.81%), α-pinene (5.27%; 4.71%). Following 4 h of treatment leaves volatile oil at doses of 250, 500 and 1000 mg/kg significantly reduced paw volume to 94, 82 and 69%, respectively. The same doses significantly reduced COX-2 activity to 73.8, 50.7 and 21.4 nmol/min/mL, respectively. A significant reduction of PGE2 concentration was observed (2.95 ± 0.2, 2.45 ± 0.15 and 1.75 ± 0.015 pg/mL). CG oil exhibited a significant modulatory effect on ethanol-induced gastritis in rats as the level of NO reduced to 32, 37 and 41 µM nitrate/g and also a significant inhibition of lipid peroxidation was observed via reduction of MDA concentration (1.15, 1.11 and 1.04 nmol/g). CONCLUSION: CG volatile oil exhibited an anti-inflammatory effect and protected against ethanol-induced non-ulcerative gastritis.

In vitro digestion, antioxidant and antiacetylcholinesterase activities of two species of Ruta: Ruta chalepensis and Ruta montana.

CONTEXT: Ruta genus (Rutaceae) is abundantly used and described in the most ancient systematic records of medical practice of the Mediterranean world. In Tunisia, this genus is represented by two medicinal and aromatic shrubs: Ruta chalepensis L. and Ruta montana L. OBJECTIVE: This study investigates the antioxidant and acetylcholinesterase inhibition (AChE) activities before and after in vitro gastrointestinal metabolism of leaf decoction of R. chalepensis and R. montana. MATERIALS AND METHODS: We study, in vitro, the effect of the gastrointestinal juices gastric (1.75 mL) or pancreatic (2.5 mL) juices, on the biological activity by the measurement of the antioxidant activity and AChE inhibition during 4 h of decoction extract obtained from the leaves of the two species of Ruta. RESULTS: The results showed that the ability to inhibit the AChE enzyme was similar; being the greatest inhibitory activity exhibited by the ethanol extract (IC50 = 12 ± 1.1 µg/mL) obtained from leaves of R. chalepensis. CONCLUSION: In conclusion, we showed that there was no appreciable degradation and that the activity was kept constant after gastric and pancreatic juice digestion.

Regulatory/modulatory effect of prune essence concentrate on intestinal function and blood lipids.

CONTEXT: Prunus domestica Linn (Rosaceae) has been considered a functional food, owing to its various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic and anticancer. OBJECTIVE: This placebo-controlled, randomized study was framed to check the beneficial activity of prune essence concentrates (PEC) in corroboration with intestinal function and lipid profile in mildly hypercholesterolemic subjects. MATERIALS AND METHODS: Sixty healthy mild hypercholesterolemic subjects were randomly chosen and segregated into three groups as placebo (consume 50 mL of simulated prune drink), PEC I (consume 50 mL of PEC/day) and PEC II (consume 100 mL of PEC/day) for 4 weeks with 2 weeks of follow-up without PEC consumption. RESULTS: Intake of PEC (I and II) for 4 weeks substantially ameliorated (p < 0.05) the colony number of Bifidobacterium spp. (1.18- and 1.19-fold) and Lactobacillus spp. (1.07- and 1.16-fold), but markedly lowered (p < 0.05) the colony number of Clostridium perfringens (5.97 and 8.35%) and Escherichia coli (6.25 and 9.38%). Meanwhile, the total cholesterol (TC; 5.90 and 6.99%) levels and LDL-c (6.68 and 6.53%) were significantly reduced (p < 0.05), but no change in other lipid parameters. Whereas, the antioxidant capacity was also concomitantly elevated (p < 0.05) upon administration with PEC. DISCUSSION AND CONCLUSION: Overall, the results suggest that the use of PEC may positively regulate the intestinal microflora and thereby effectively lower the TC levels and thus act as a hypocholesterolemic agent.

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats.

CONTEXT: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders. OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats. MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon. RESULTS: APME or APAE pretreatment significantly (p < .05-.001) prevented AA-induced reduction in body weight and increase in colitis parameters viz. stool consistency, colon weight/length ratio and ulcer score, area and index. Extracts treatment attenuated (p < .001) increase in alkaline phosphatase and lactate dehydrogenase in serum and myeloperoxidase activity and cytokines in colon tissue due to AA administration. Extracts treatment prevented AA-induced elevation in lipid peroxidation and decline in activities of superoxide dismutase and catalase and reduced-glutathione content (p < .05-.001) along with histopathological alterations. PRDS also showed similar ameliorative effect on colitis. DISCUSSION AND CONCLUSION: APME and APAE showed a preventive effect on UC, and ameliorated inflammation and oxidative damage in colon. The effects may be attributed to presence of phytochemicals, betulinic acid, ß-sitosterol, and glucomannan. In conclusion, the tuber of Amorphophallus paeoniifolius exhibited an anticolitic effect through anti-inflammatory and antioxidant action.

Prophylactic and therapeutic effect of Punica granatum in trinitrobenzene sulfonic acid induced inflammation in rats.

Pomegranate (Punica granatum L., Punicaceae) contains varieties of antioxidants and phytochemicals; there are evidences that phytochemicals and antioxidants play a vital role in reducing inflammation. Hence this investigation was planned to assess the outcome of Punica granatum on trinitrobenzene sulfonic acid provoked colitis in rats at 2, 5 and 8ml/kg of the body weight. The effect of P. granatum was assessed in two group i.e. prophylaxis as pre-colitis and therapeutic as post-colitis. After completion of dosing in both the groups, macroscopic and histological examination of colon was carried out along with estimation of serum myeloperoxidase, glutathione, alkaline phosphate, fibrinogen and C-reactive protein. In prophylactic procedure P. granatum revealed significant (P<0.05) changes in biochemical markers of inflammation at 5 and 8ml/kg doses. However in therapeutic procedure significant change was observed only at 8ml/kg. Thus results of the present study suggest that P. granatum have a role in prevention as well as treatment of inflammation.

Isolation and evaluation of the myorelaxant effect of bergapten on isolated rat jejunum.

CONTEXT: Plants of the genus Heracleum L. (Apiaceae) have a long history of being used in traditional medicines for the treatment of alimentary tract disorders, and these biological effects have been ascribed to the presence of furanocoumarins (including bergapten). OBJECTIVES: This study aimed to develop an efficient, preparative, counter-current chromatographic separation of bergapten in order to characterize its spasmolytic activity in isolated rat jejunum strips. MATERIALS AND METHODS: Successful separation of the dichloromethane extract of the fruits of Heracleum leskovii Grossh. was achieved by high-performance countercurrent chromatography (HPCCC) using a two-phase solvent system composed of n-heptane/EtOAc/MeOH/H2O (6:5:6:5, v/v/v/v). The pharmacological assessment of bergapten (0.0001-50 µM) on jejunum smooth muscle strips isolated from rats was conducted under isotonic conditions, following up to three hours of incubation. RESULTS: The separation method was scaled up six-fold from analytical to semi-preparative conditions, affording bergapten of >99% purity in less than 30 min. This permitted bergapten to be available in quantity for spasmolytic tests on isolated jejunum strips from rats. Bergapten caused myorelaxation of the intestine preparations in the concentration range of 0.0001-1 µM. At higher doses, bergapten caused either relaxation or contraction of the smooth muscle. DISCUSSION AND CONCLUSION: Bergapten was successfully isolated by rapid HPCCC and its spasmolytic activity was confirmed, thereby providing a preliminary evidence base for the traditional medicine application. The data suggest that bergapten causes no irreversible changes to intestinal tissue.

Antioxidant capacity of broccoli sprouts subjected to gastrointestinal digestion.

BACKGROUND: Broccoli is a common vegetable recognized as a rich source of antioxidants. To date, research on the antioxidant properties of broccoli, predominantly conducted on extracts, has not considered the lesions of composition and this activity after gastrointestinal digestion. Here the stability of antioxidants during gastrointestinal digestion was evaluated in conjunction with the protective effects of broccoli sprouts (BS) against oxidative stress in human colon cells. RESULTS: The obtained data suggest that, among the biocompounds identified in BS, glucosinolates were mainly degraded under gastrointestinal digestion, while phenolics, particularly hydroxycinnamic acid derivatives, were the most resistant constituents. The antioxidant capacity of BS extract subjected to gastrointestinal digestion was similar to or higher than that determined for non-digested BS. Gastrointestinal digested BS extract exhibited reactive oxygen species (ROS)-inhibitory capacity in NCM460 human colon cells, with 1 mg mL(-1) showing an ROS clearance of 76.59%. A 57.33% reduction in oxidative DNA damage in NCM460 cells due to treatment with digested BS extract was observed. CONCLUSION: The results lend support to the possible application of BS as a rich source of antioxidants to improve the defensive system against oxidative stress in the human colon mucosa.

Potential of the plant Thespesia populnea in the treatment of ulcerative colitis.

CONTEXT: Thespesia populnea Sol. ex Correa (Malvaceae), an indigenous tree species in India, is of interest to researchers because traditionally its heartwood is used in the treatment of ulcer and colic pain. OBJECTIVE: To validate its folk use in the treatment of ulcerative colitis (UC). MATERIALS AND METHODS: Mice were administered intrarectal DNBS and then treated with different plant extracts (100 and 200 mg/kg), 30 min before and 24 and 48 h after DNBS infusion. Colonic mucosal injury was assessed by macroscopic and histological examination. Furthermore, malondialdehyde (MDA), myeloperoxidase (MPO), protease, and hemoglobin (Hb) contents were measured in tissue and blood samples. RESULTS: Administration of various extracts ameliorated macroscopic and microscopic scores which were altered due to DNBS treatment in mice. Hb concentration in blood was restored significantly by the aqueous extract to 17.20 ± 0.5, which was reduced to 13.80 ± 0.5 after treatment with DNBS. MDA level was increased to 10.82 nm/mg and 10.25 nm/ml in tissue and blood, respectively, due to DNBS treatment which was reduced to 2.69 nm/mg and 3.59 nm/ml in tissue and blood, respectively, by aqueous extract treatment. Similarly, MPO level was increased to 412 U/mg and 404 U/ml in tissue and blood, respectively, which was significantly reduced to 205 U/mg and 219 U/ml in tissue and blood, respectively, by aqueous extract treatment. Aqueous extract significantly reduced protease activity which was markedly increased in DNBS-treated animals. DISCUSSION AND CONCLUSION: Aqueous extract of heartwood of T. populnea is effective in the treatment of UC.

Industrial hemp decreases intestinal motility stronger than indian hemp in mice.

BACKGROUND: Indian hemp has shown beneficial effects in various gastrointestinal conditions but it is not widely accepted due to high content of tetrahydrocannabinol resulting in unwanted psychotropic effects. AIM: Since industrial hemp rich in cannabidiol lacks psychotropic effects the aim of research was to study the effects of industrial hemp on intestinal motility. MATERIALS AND METHODS: Animals were randomly divided in six groups (each group consisting of 6 animals): Control group, Cind group - receiving indian hemp infuse for 20 days, Cids group-receiving industrial hemp infuse for 20 days, M group - treated with single dose of morphine (5 mg/kg i.m.) Cind+M group - treated with indian hemp infuse and single dose of morphine (5 mg/kg i.m.), Cids+M - treated with industrial hemp infuse and single dose of morphine (5 mg/kg i.m.). On the 20th day of the study animals were administered charcoal meal, and were sacrificed 35 minutes after administration. Intestinal motility was estimated according to distance between carbo medicinalis and cecum in centimeters. RESULTS: Decrease of intestinal motility in animals treated with indian hemp infuse was not significant compared to controls and it was smaller compared to animals treated with morphine (Indian hemp =15.43±10.5 cm, morphine = 20.14±5.87 cm). Strongest decrease of intestinal motility was recorded in animals treated with industrial hemp infuse, and it was significant compared to controls and morphine (industrial hemp = 26.5±9.90 cm, morphine = 20.14±5.87 cm; p < 0.005). CONCLUSIONS: Although not completely without psychotropic activity cannabidiol could be a potential replacement for tetrahydrocannabinol. Since industrial hemp infuse rich in cannabidiol reduces intestinal motility in healthy mice cannabidiol should be further evaluated for the treatment of intestinal hypermotility.

Anti-inflammatory, gastroprotective, and cytotoxic effects of Sideritis scardica extracts.

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity.

Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis.

Huangqin decoction (HQD) is a Traditional Chinese Medicine formula for ulcerative colitis. However, the pharmacology and molecular mechanism of HQD on ulcerative colitis is still unclear. Combined microarray analysis, network pharmacology, and molecular docking for revealing the therapeutic targets and molecular mechanism of HQD against ulcerative colitis. TCMSP, DrugBank, Swiss Target Prediction were utilized to search the active components and effective targets of HQD. Ulcerative colitis effective targets were obtained by microarray data from the GEO database (GSE107499). Co-targets between HQD and ulcerative colitis are obtained by Draw Venn Diagram. PPI (Protein-protein interaction) network was constructed by the STRING database. To obtain the core target, topological analysis is exploited by Cytoscape 3.7.2. GO and KEGG enrichment pathway analysis was performed to Metascape platform, and molecular docking through Autodock Vina 1.1.2 finished. 161 active components with 486 effective targets of HQD were screened. 1542 ulcerative colitis effective targets were obtained with |Log2FC|> 1 and adjusted P-value < 0.05. The Venn analysis was contained 79 co-targets. Enrichment analysis showed that HQD played a role in TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, etc. IL6, TNF, IL1B, PTGS2, ESR1, and PPARG with the highest degree from PPI network were successfully docked with 19 core components of HQD, respectively. According to ZINC15 database, quercetin (ZINC4175638), baicalein (ZINC3871633), and wogonin (ZINC899093) recognized as key compounds of HQD on ulcerative colitis. PTGS2, ESR1, and PPARG are potential therapeutic targets of HQD. HQD can act on multiple targets through multi-pathway, to carry out its therapeutic role in ulcerative colitis.

The essential oil of Eucalyptus tereticornis and its constituents, α- and ß-pinene, show accelerative properties on rat gastrointestinal transit.

The essential oil of Eucalyptus tereticornis (EOET) has pharmacological activities but their effects on the gastrointestinal tract are yet unknown. It possesses α- and ß-pinene as minor constituents, isomers largely used as food or drink additives. In this work, we studied their actions on gut motility. After feeding with a liquid test meal, conscious rats received perorally EOET, α-, or ß-pinene, and the fractional dye retention was determined. EOET and its constituents decreased the gastric retention. In anesthetized rats, pinenes increased gastric tonus, while enhancing the meal progression in the small intestine of conscious rats. Both α- and ß-pinene contracted gastric strips IN VITRO but relaxed the duodenum. Conversely, EOET relaxed both the gastric and duodenal strips. In conclusion, EOET accelerates the gastric emptying of liquid, and part of its action is attributed to the contrasting effects induced by α- and ß-pinene on the gut.

Gastroprotective activity of kaempferol glycosides from Malvaviscus arboreus Cav.

ETHNOPHARMACOLOGICAL RELEVANCE: Malvaviscus arboreus is traditionally used in Mexico and Central America for culinary and medicinal purposes. Leaves and flowers of this species are commonly used for preparation of salads, herbal teas and herbal dyes. Panamanian, Guatemalan and Mexican healers use this medicinal plant for the management of fever, respiratory complications, dysentery, liver and gallbladder problems, stomachache and gastritis between other health troubles. AIM OF THE STUDY: Considering the traditional use of M. arboreous as well as its content in flavonoids and other polyphenols, the objective of this work was to evaluate the gastroprotective effect of an aqueous extract and identify the potential bio-active principles from flowers of this species. MATERIAL AND METHODS: Fresh flowers of Malvaviscus arboreus were collected, dried, and macerated with water. The aqueous extract (ExAq) was partitioned using an immiscible mixture of water and ethyl acetate, giving an aqueous (MaAq) and organic (MaEA) fractions. The gastroprotective effect was carried out using an ethanol-induced gastric ulcer experimental test in male rats. While tween 20 was used as a negative control, famotidine (10 mg/kg) and L-arginine (300 mg/kg) were used as positive controls. Compounds 1 and 2 were isolated by several chromatographic techniques and the chemical characterization was carried out by means of the analysis of the NMR spectra in one and two dimensions. RESULTS: The integrate extract (ExAq) to 250, 500 and 750 mg/kg showed gastroprotective effect with high levels of 97.8%, 79.5% and 91.1% respectively. The organic fraction (MaEA) displayed a protection of 91.2%, 96.0% and 99.4% when it was evaluated at 125, 250 and 500 mg/kg respectively. Comparison of these results with famotidine at 10 mg/kg (83% of gastroprotection) indicated that ethyl acetate fraction showed a better gastroprotection. The bio-guided separation of this organic mixture, allowed obtaining the most active fraction (C1F4, 60 mg/kg) which was finally purified to obtain two glycosylated flavonols: kaempferol 3-O-D-sophoroside (1) and kaempferol 3-O-D-sambubioside (2). This mixture of flavonoids (40 y 60 mg/kg) showed 93.7 and 92% of gastroprotective activity respectively. CONCLUSION: This study allowed demonstrating that an aqueous extract and its organic fraction (MaEA) from M. arboreous contain glycosylated flavonoids (1 and 2) which are responsible of the gastroprotective properties of M. arboreous. These results will be used in the future development of a standardized treatment useful in the therapeutic management of gastric ulcers.

Genus Gentiana: A review on phytochemistry, pharmacology and molecular mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: As the largest genus of Gentianaceae family, the Gentiana genus harbors over 400 species, widely distributed in the alpine areas of temperate regions worldwide. Plants from Gentiana genus are traditionally used to treat a wide variety of diseases including easing pain dispelling rheumatism, and treating liver jaundice, chronic pharyngitis and arthritis in China since ancient times. In this review, a systematic and constructive overview of the traditional uses, phytochemistry, molecular mechanisms, toxicology and pharmacological activities of the researched species of genus Gentiana is provided. MATERIALS AND METHODS: The used information in this review is based on various databases (PubMed, Science Direct, Wiley online library, Wanfang Data, Web of Science) through a search using the keyword "Gentiana" in the period of 1981-2019. Besides, other ethnopharmacological information was acquired from Chinese herbal classic books and Chinese pharmacopoeia 2015 edition. RESULTS: The plants from Gentiana genus have a long tradition of various medicinal uses in Europe and Asia. Phytochemical studies showed that the main bioactive components isolated from this genus includes iridoids xanthones and flavonoids. These compounds and extracts isolated from this genus show a wide range of protective activities including hepatic protection, gastrointestinal protection, cardiovascular protection, immunomodulation, joint protection, pulmonary protection, bone protection and reproductive protection. Molecular mechanism studies also indicated several potential therapeutic targets in the treatment of certain diseases by plants from this genus. Besides, natural products from this plant show no significant animal toxicity, cytotoxicity or genotoxicity. CONCLUSION: This review summarized the traditional medicinal uses, phytochemistry, pharmacology, toxicology and molecular mechanism of genus Gentiana, providing references and research tendency for plant-based drug development and further clinical studies.

The medicinal properties of Cassia fistula L: A review.

Medicinal plant species contain vast and unexploited riches of chemical substances with high medical potential making these plant species valuable as biomedicine sources. Cassia fistula L is an important medicinal plant used in many traditional medicinal systems including Ayurveda and Chinese Traditional Medicine. It is a deciduous medium sized tree with elongated and rod-shaped fruits having pulp and have bright yellow flowers, earning the name 'Yellow Shower'. The present review provides a version of updated information on its botanical description and pharmacological properties including antioxidant, antimicrobial, anti-inflammatory, antidiabetic, antitumor, hepatoprotective among other activities. Pharmacological reviews on medicinal plants will provide valuable information; thus, Cassia fistula L can provide important discoveries of valuable bioactive natural products facilitating in developing novel pharmaceuticals products.

Limonene from Agastache mexicana essential oil produces antinociceptive effects, gastrointestinal protection and improves experimental ulcerative colitis.

ETHNOPHARMACOLOGY RELEVANCE: Agastache mexicana is a popular plant of great demand in folk medicine, essentially due to its calming properties and for alleviating arthritic, muscular and abdominal pain. Despite its spectrum for pain relief, pharmacological studies of its bioactive constituents have been barely investigated. AIM OF THE STUDY: To evaluate protective properties of the A. mexicana and bioactive compounds improving pathological gastrointestinal conditions in rodents. MATERIAL AND METHODS: Different doses of the essential oil of A. mexicana ssp. mexicana and ssp. xolocotziana (30-562.2 mg/kg, i.p.) and individual monoterpenes (3-300 mg/kg, i.p.) were evaluated in an abdominal pain model. The most active monoterpene limonene and sulfasalazine (reference drug, 100 mg/kg, p.o.) were also evaluated in the oxazolone-induced colitis model using an oral gavage, where some inflammatory cytokines were analyzed by enzyme-linked immunosorbent assays. Finally, colonic histological assessment and gastroprotection in the absolute ethanol-induced ulcer model were explored. RESULTS: Our results demonstrated that the essential oil of both subspecies produced a significant reduction in the abdominal writhes, where monoterpenes limonene and pulegone were partially responsible bioactive metabolites. Limonene showed the major antinociceptive efficacy in the writhing test. It also significantly decreased hyperalgesia, pathological biomarkers, and colonic inflammatory cytokines in the oxazolone-induced colitis model, as well as prevention in gastric damage. CONCLUSIONS: Present results provide scientific evidence to reinforce the use of A. mexicana in the traditional medicine for gastrointestinal conditions, mainly related to pain and inflammation, demonstrating the potential of monoterpenes as natural products in the therapeutics of gastrointestinal affections such as ulcer, colitis, and abdominal pain.