Chinese sumac (Rhus chinensis Mill.) fruits alleviate indomethacin-induced gastric ulcer in mice by improving oxidative stress, inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine and a previous literature, many parts of Chinese sumac (Rhus chinensis Mill.), including fruits, are used as traditional herb to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. However, the effects of the fruits on the prevention of gastric ulcer and the underlying mechanisms have not been reported. AIM OF THE STUDY: This experiment aimed to investigate the preventive effect of ethanol extract (RM) from Chinese sumac fruits on indomethacin-induced gastric ulcer in mice and the underlying mechanisms. MATERIALS AND METHODS: A single gavage of indomethacin was used to induce a gastric ulcer model in Kunming male mice. According to the results of histopathological analysis, immunohistochemistry and immunofluorescence analysis, as well as the expression of prostaglandin E-2, antioxidant enzymes and cytokines, the protective effect of RM on indomethacin-induced gastric ulcer was evaluated. The expression levels of several key proteins involved in oxidative stress, inflammation and apoptosis in gastric tissue were detected to illuminate the underlying mechanisms. RESULTS: RM significantly reduced the ulcer index and pepsin activity, improved the microstructure of gastric mucosa and the prostaglandin E-2 content, restored the levels of glutathione and superoxide dismutase, and decreased the contents of malondialdehyde, advanced oxidation protein products, TNF-α, IL-1 ß and IL-6. Further experimental results showed that RM could improve the expression levels of HO-1 and NQO1 by activating the Nrf2 protein pathway to alleviate oxidative stress in gastric tissue. At the same time, RM significantly down-regulated the expressions of p-NF-κB, p-IκBα and iNOS to relieve inflammatory response, and inhibited the cellular apoptosis of gastric tissue by up-regulating Bcl-2 and down-regulating Bax and cleaved Caspase-3. CONCLUSIONS: The current work clarified that the ethanol extract from Chinese sumac fruits can improve the oxidative stress level, inflammatory response and cell apoptosis in gastric tissue by interfering with the expressions of several key regulatory proteins to prevent indomethacin-induced gastric ulcer in mice. This study may provide some insights and scientific evidence on the application of Chinese sumac fruits as a traditional herb to prevent or alleviate gastric ulcer.

Gastroprotective effects of extract of Jasminum grandiflorum L. flower in HCl/EtOH-induced gastric mucosal ulceration mice.

Jasminum grandiflorum L. is a medicinal plant used to treat hepatitis and gastritis, but the mechanisms underlying its protective effects against gastrointestinal mucosal damage remain to be elucidated. In this study, we analyzed the effects of four different extracts and two compounds from the flower of J. grandiflorum in a mouse model of HCl/EtOH-induced gastric ulcer. The flower extracts alleviated gastric mucosal ulceration by increasing PGE2 production and the activity of antioxidant enzymes, along with the suppression of reactive oxygen species (ROS) generation, lipid peroxidation, apoptosis-related proteins, pro-inflammatory cytokines and nitric oxide (NO) production.

Evaluation of antioxidant and anti-ulcerogenic effects of Eremurus persicus (Jaub & Spach) Boiss leaf hydroalcoholic extract on ethanol-induced gastric ulcer in rats.

This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180-220 g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250 mg/kg plant extract, and group recipient the dose of 500 mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1 ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced (P < 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO· and GSH levels. EPE also was able to decrease the levels of ROS, MDA, PCO and serum NO·. According to the results, it can be concluded that pre-treatment with EPE prevents the formation of gastric ulcers caused by ethanol, which can be attributed to the antioxidant activity of plant polyphenols compounds.

Chemical Constituents and Anti-Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair.

The essential oil (EO) of the herbal pair (HP), Alpinia officinarum-Cyperus rotundus (HP G-X) has been conventionally used in traditional Chinese medicine (TCM) for 'warming the stomach' and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti-gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G-X and its corresponding single herbs were analyzed using GC/MS. A total of 74, 56, and 85 compounds were detected in A. officinarum (GLJ), C. rotundus (XF), and HP G-X, accounting for 93.2 %, 89.5 %, and 92.0 % of the total content, respectively. GLJ mainly contains 1,8-cineol (22.0 %) and α-terpineol (11.8 %), whereas cyperenone (22.4 %) and cyperene (12.3 %) were the major constituents in XF. These four compounds were also detected in the HP G-X with relatively high composition as 11.8 %, 5.5 %, 11.8 %, and 10.6 %, respectively. Although no new compounds were detected in HP G-X, the relative concentration of some compounds increased, while others decreased or even disappeared. HP G-X showed the lowest toxicity (TC50 >800 µg/mL) against human gastric mucosal epithelial cells (GES-1) and had the best protective effect against ethanol-induced GES-1 cell damage compared to the individual herbs. In vitro studies demonstrated that HP G-X and the corresponding single herbs significantly reduced IL-6, TNF-α, and COX-2. In addition, in vivo investigations indicated that HP G-X can protect the gastric mucosa of mice from ethanol-induced damage by inhibiting the inflammatory reaction and providing analgesia. It can also inhibit the expression of NF-κBp65, COX-2, and TRPV1 protein, reduce the concentrations of IL-6 and TNF-α, and relieve heat-induced pain. This study further substantiated the traditional application of HP G-X against gastric ulcers through both in vivo and in vitro investigations.

Eremomastax speciosa (Hochst.) Cufod. counteracts the delaying effect of indomethacin on Helicobacter pylori-associated chronic gastric ulcers healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Information collected from local traditional healers reported that Eremomastax speciosa (Hochst.) Cufod. has for a long time been used to manage gastric ulcers in many regions of Cameroon and beyond. This traditional use is supported by numerous studies. However, efficacy of this plant has never been tested in case of chronic gastric ulcers associating Helicobacter pylori infection. AIM OF THE STUDY: This study was designed to investigate curative effects of the aqueous extract of E. speciosa leaves (AEESL) against chronic gastric ulcers associated to Helicobacter pylori infection. MATERIALS AND METHODS: Two experimental methods of chronic gastric ulcers, involving H. pylori infection, were performed using Wistar rats, namely: acetic acid-induced ulcers and "unhealed ulcers". E. speciosa extract was tested at three doses (100; 200; 400 mg/kg) and at the end of experiments, some in vivo antioxidant parameters were measured, bacterial load in stomach tissue calculated and histopathological examinations performed. RESULTS: E. speciosa reduced ulcer index at all the doses and significantly increased mucus production as well as antioxidant (mainly SOD and GSH) level. Bacterial load in stomach significantly decreased (p < 0.05) in extract-treated groups (200 and 400 mg/kg) as confirmed by histopathological observations. The extract was found to be non toxic to healthy and cancerous cells (IC50 > 1000 µg/mL). CONCLUSIONS: E. speciosa accelerated healing of gastric ulcers even in presence of indomethacin, while decreasing bacterial loads in rats' stomachs. These results provide supplementary support to the use of E. speciosa in ethnomedicine and open new perspectives regarding development of a herbal-based monotherapy able to efficiently replace/supplement standard antiulcer tri/quadritherapy.

Evaluation of the Gastroprotective Effect of the Flavonoid Complex from Lychnis chalcedonica L. on the Models of Experimental Ulcerogenesis.

Using rat and mouse models of neurogenic, ethanol-induced, and indometacin-induced damage to the gastric mucosa we demonstrated that course preventive treatment with flavonoid complex from aerial parts of Lychnis chalcedonica L. increased the resistance of gastric mucosa to ulcerogenic factors of different etiology. The gastroprotective effect of the phytocomplex in a dose range of 16-1600 µg/kg was comparable with that of the reference drug plantaglucide and was superior to that of the reference drugs eleutherococcus extract and methyluracil in the therapeutic doses. The antiulcerogenic activity of Lychnis chalcedonica flavonoid complex considerably exceeded activity of Lychnis chalcedonica L. extract demonstrated in our previous experiments.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction.

Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p < 0.001) inhibited gastric lesions and malondealdehyde (MDA) levels and upregulated antioxidant enzymes level. Furthermore, nine compounds were documented as bioactive, displayed good binding affinities to against gastric H+-K+ATPase enzyme while these compounds illustrated inhibitory effect. From these studies, it is established MEBLL has ulcer healing property as unveiled by in vivo and in silico studies.

Phytochemicals and biological properties of Annona coriacea Mart. (Annonaceae): A systematic review from 1971 to 2020.

Annona coriacea Mart., popularly known as "marolo", "araticum" and "araticum-liso" is a species distributed in Paraguay and Brazil, and easily found in Caatinga, Cerrado, and Pantanal biomes. The araticum has been used in folk medicine to treat stomatitis, neuralgia, rheumatism, headaches, furuncle, ulcers, and dermatitis. This systematic review aimed to provide a comprehensive overview of the ethnomedicinal use, phytochemistry, and pharmacological activity of A. coriacea. A search for scientific articles of electronic databases (Science Direct, PubMed, Lilacs, Scopus, Google Scholar, Scielo, and Web of Science) was performed identifying studies published until November 2020. All papers considering traditional medicinal uses, phytochemistry, and pharmacological properties were included. Forty-six articles (n = 212 subjects) met the inclusion criteria set for this review. Of the 46 articles reviewed, 34 were focused on biological activity investigations, while 12 were limited to phytochemical studies. These studies showed the presence of a diversity of secondary metabolites such as acetogenins, sesquiterpenes, alkaloids, flavonoids, and diterpenes. To date, pharmacological tests have demonstrated significant biological activities of this plant, being the most promising anticancer, anti-inflammatory, antiulcer, and insecticide activities. Additionally, the medicinal utilization of A. coriacea appears to be promising, supporting its possible uses for human health with antioxidant, anxiolytic, antiulcer, insecticide, and antiparasitic activities. Ultimately, comprehensive studies involving clinical trials are required to validate the existing traditional practices and their related health benefits scientifically.

Anti-Ulcerogenic and Cytoprotective Effects of Saharian (Sidr) Honey from Algeria.

AIM AND OBJECTIVE: This study aimed at investigating the gastro-protective effects of Algerian Sahara (Sidr) honey from Apis mellifera intermissa against HCl/Ethanol-induced gastric ulcers in rats. MATERIALS AND METHODS: Total phenolic content, antioxidant activity and phenolic compounds were determined. Then, three groups of rats (control, HCl/ Ethanol-induced ulcer, and orally administered honey) were used for the determination of gastro-protective effect of Sidr honey. RESULTS: Total phenolic content, total flavonoid content, and DPPH activity of the honey sample were determined as 47.35±3.35 mg GAE/ 100 g, 2.13±0.17 mg QE/ 100 g, and 229.24±0.02 mg/mL, respectively. Oral pretreatment of rats with honey (1.2 g/Kg body weight orally at an interval of 2 days) protected gastric mucosa against HCl/Ethanol-induced damage by decreasing ulcer score, the volume and acidity of gastric juice and increasing pH. CONCLUSION: These results were confirmed by the histological assessment, which demonstrated a significant gastro-protective activity of Saharian (Sidr) honey against HCl/Ethanol-induced stomach ulcer. Plasma tumor necrosis factor-α, IL-6 and PGE2 were also measured. Sahara honey significantly decreased the plasma TNF-α, PGE2, and IL-6 concentrations.

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.

The gastroprotective effect of red propolis extract from Northeastern Brazil and the role of its isolated compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used in folk medicine to treat gastric disorders for centuries. However, although studies have been conducted to validate the gastroprotective and anti-ulcer activity of some types of propolis, red propolis activity remains unknown. AIM OF THE STUDY: The present study aimed to evaluate the gastroprotective effect of the hydroalcoholic extract of red propolis (HERP), its mode of action, and the main compounds involved in its activity, therefore contributing to validate the chemical and pharmacological potential of this product. MATERIAL AND METHODS: The effect of HERP (30, 100 and 300 mg/kg p.o. and 30 mg/kg i.p.), and the isolated compounds vestitol (VS), neovestitol (NV), methylvestitol (MV), medicarpin (MD), and oblongifolin AB (OB) (10 mg/kg p.o.) were evaluated on gastric ulcers induced by 60% ethanol/0.3 M HCl (5 mL/kg, p.o.) in mice. Histological changes and mucin levels were assessed by HE and PAS, respectively. Moreover, oxidative stress parameters and myeloperoxidase activity were analyzed on ulcerated tissue. The effect of HERP on gastric acid secretion was evaluated by pyloric ligature model and the mechanisms involved in its gastroprotective effect were investigated by pretreating mice with L-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a non-selective cyclooxygenase inhibitor, 10 mg/kg, i.p.). RESULTS: HERP (300 mg/kg p.o. or 30 mg/kg i.p.), MV, and MD (10 mg/kg p.o.) protected gastric mucosa against the damage induced by ethanol/HCl. Histological changes were attenuated by the HERP, MV, and MD. Moreover, HERP and MV increased mucin levels. Besides, oxidative stress and MPO activity were reduced by the three treatments. HERP did not display anti-secretory action, but its effect was abolished by indomethacin treatment. CONCLUSIONS: HERP displays gastroprotective property against ethanol/HCl-induced damage. Its effect is dependent on prostaglandins and mucin production. The compounds MV and MD may have an essential role in the activity of HERP. Our data contribute to validate the traditional use of propolis for gastric disorders.

Chemical constituents of the antiulcer purified fractions of Lindera reflexa Hemsl. and its quantitative analysis.

The root of Lindera reflexa Hemsl. (LR) is a folk Chinses herbal medicine that has been used to treat gastritis and peptic ulcers. In this study, three new stilbenes (1-3) and two known flavonoids (4 and 5) were isolated from the antiulcer purified fractions of LR. The chemical structures of the isolated compounds were characterized comprehensively based on the basis of extensive spectroscopic data. Absolute configurations of compounds 1, 2, and 3 were determined by ECD calculations. The cytotoxic activities of compounds 1-5 were evaluated by MTT assay. Compound 4 showed the strongest inhibitory effect on the proliferation of tumor cells lines MGC803 and SMMC-7721, with IC50 values of 2.65 and 4.13 µM, respectively. The quantitative analysis of 12 compounds of the antiulcer purified fractions of LR were carried out by using the reversed-phase high-performance liquid chromatography (HPLC) method. Within the test range, all calibration curves showed good linearity (R2 > 0.9993). The LOD, LOQ, specificity, precision, and accuracy of the method were verified. Therefore, the present study may provide a valuable method for quality control the antiulcer purified fractions of LR.

Sphaeranthus senegalensis DC: Evaluation of chemical constituents, oral safety, gastroprotective activity, and mechanism of action of its hydroethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Sphaeranthus senegalensis DC is a seasonal herb with a spicy smell that grows wild in wet grounds of tropical Africa and Asia. The plant is used in folk medicine for the treatment of various diseases; that includes its use to treat gastric ulcers. AIM OF THE STUDY: This study aimed to investigate the chemical constituents of the hydroethanolic extract of Sphaeranthus senegalensis DC and evaluate its oral safety, gastroprotective activity, and mechanisms of action using laboratory models in rats and mice. MATERIALS AND METHODS: Hydroethanolic extract (70%) of the powdered whole dried material was prepared, and chemical constituents of the resultant extract (denoted HESs) standardized using the high-performance liquid chromatography (HPLC) method. The safety profile of HESs was assessed using 2000 mg/kg, oral (p.o.) for Hippocratic screening in mice, and 800 mg/kg, p.o. for 28 days subchronic toxicity assay in rats. The gastroprotective effect of HESs (25, 100, and 400 mg/kg, p.o.) was investigated using acidified ethanol, piroxicam, water immobilization stress, and acetic acid-induced ulcer models. The gastroprotective mechanisms of HESs were evaluated using its effect on gastric mucus protection, nitric oxide modulation, gastric juice secretory parameters, catalase and myeloperoxidase activities. Histological analysis of the stomach tissues was also carried out. RESULTS: The HPLC analysis indicated the presence of 25.94% phenolics (gallic acid, caffeic acid, and ferulic acid) and 14.53% flavonoids (rutin, morin, luteolin, quercetin, and apigenin). Hippocratic screening and the 28 days subchronic study indicated that HESs is generally safe. Result shows that oral administration of HESs (25, 100 and 400 mg/kg) alleviated the severity of the gastric ulcers induced by acidified ethanol by 35.65% (p < 0.05), 48.70% (p < 0.05) and 78.02% (p < 0.001) respectively; exhibited gastroprotective effect against the gastric lesions induced by piroxicam by 37.97% (p < 0.05), 53.27% (p < 0.05) and 76.23% (p < 0.001) respectively; and decreased the severity of the water immobilization stress-induced gastric ulcers by 32.43% (p < 0.05), 55.26% (p < 0.01) and 74.05% (p < 0.001) respectively, when compared to the vehicle control group. The mechanisms of action assays indicated that the gastroprotective activity was mediated mainly through gastroprotection, antisecretory, and antioxidant activities. Histological analysis showed it inhibited epithelial cell loss, vascular damage, and leucocyte infiltration. CONCLUSION: HESs contains useful phytochemicals, is safe, and exhibited significant gastroprotective action. The results provided justification for its claim in the treatment of gastric ulcers and its evaluation for potential application as a gastroprotective agent.

Subtribe Hyptidinae (Lamiaceae): A promising source of bioactive metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: The subtribe Hyptidinae contains approximately 400 accepted species distributed in 19 genera (Hyptis, Eriope, Condea, Cantinoa, Mesosphaerum, Cyanocephalus, Hypenia, Hyptidendron, Oocephalus, Medusantha, Gymneia, Marsypianthes, Leptohyptis, Martianthus, Asterohyptis, Eplingiella, Physominthe, Eriopidion and Rhaphiodon). This is the Lamiaceae clade with the largest number of species in Brazil and high rates of endemism. Some species have been used in different parts of the world mainly as insecticides/pest repellents, wound healing and pain-relief agents, as well as for the treatment of respiratory and gastrointestinal disorders. AIM OF THE REVIEW: This review aims to discuss the current status concerning the taxonomy, ethnobotanical uses, phytochemistry and biological properties of species which compose the subtribe Hyptidinae. MATERIALS AND METHODS: The available information was collected from scientific databases (ScienceDirect, Pubmed, Web of Science, Scopus, Google Scholar, ChemSpider, SciFinder ACS Publications, Wiley Online Library), as well as other literature sources (e.g. books, theses). RESULTS: The phytochemical investigations of plants of this subtribe have led to the identification of almost 300 chemical constituents of different classes such as diterpenes, triterpenes, lignans, α-pyrones, flavonoids, phenolic acids and monoterpenes and sesquiterpenes, as components of essential oils. Extracts, essential oils and isolated compounds showed a series of biological activities such as insecticide/repellent, antimicrobial and antinociceptive, justifying some of the popular uses of the plants. In addition, a very relevant fact is that several species produce podophyllotoxin and related lignans. CONCLUSION: Several species of Hyptidinae are used in folk medicine for treating many diseases but only a small fraction of the species has been explored and most of the traditional uses have not been validated by current investigations. In addition, the species of the subtribe appear to be very promising as alternative sources of podophyllotoxin-like lignans which are the lead compounds for the semi-synthesis of teniposide and etoposide, important antineoplastic agents. Thus, there is a wide-open door for future studies, both to support the popular uses of the plants and to find new biologically active compounds in this large number of species not yet explored.

Gastroprotective and cicatrizing activity of the Ziziphus joazeiro Mart. leaf hydroalcoholic extract.

Ziziphus joazeiro Mart., popularly known as 'juazeiro', is a species used in popular medicine for the treatment of bronchitis, gastric ulcers, skin wounds, and in the manufacture of cosmetic and food products. The objective of this study is to evaluate the gastroprotective and cicatrizing activity of the Z. joazeiro Mart. leaf hydroalcoholic extract (EHFZJ). The acute pre-clinical toxicity was determined by the single administration of the EHFZJ (2000 mg/kg/p.o.) and by assessing clinical signs of toxicity, according to established criteria by Malone, or mortality. Gastroprotective activity was identified through classical models of acute gastric lesions induced by indomethacin, absolute and acidified ethanol (100, 200 and 400 mg/kg/per os) and the physical barrier mechanism (400 mg/kg/per os or intraperitoneally). The cicatrizing activity of the EHFZJ was investigated by measuring the speed of wound closure and the percentage of contraction. The acute pre-clinical toxicity of EHFZJ showed no signs of toxicity and mortality. The EHFZJ demonstrated a gastroprotective effect at the 400 mg/kg dose in the classical models of acute gastric injury induced by indomethacin, absolute and acidified ethanol. The EHFZJ administration (orally) demonstrated significant inhibition, suggesting a possible physical barrier mechanism exists. The EHFZJ showed no significant differences in terms of percentage of contraction or the speed of wound closure during the observation times (0, 3, 7, 11 and 14 days). The results obtained in this study provide evidence of a potential gastroprotective activity for the Ziziphus joazeiro Mart. Leaf hydroalcoholic extract.

Protective effects of total flavonoids from Alpinia officinarum rhizoma against ethanol-induced gastric ulcer in vivo and in vitro.

CONTEXT: Alpinia officinarum Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases. OBJECTIVE: To investigate the potential protective mechanism of total flavonoids from the rhizomes of A. officinarum (F-AOH) in ethanol-induced acute gastric in vivo and in vitro. MATERIALS AND METHODS: In vivo: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). In vitro: Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 µg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1ß was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test. RESULTS: F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1ß, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC50) of F-AOH on cell damage was 17 µg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1ß and iNOS proteins. CONCLUSIONS: F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.

Chemical profile and gastroprotective effect of Jatropha elliptica (Pohl) Oken roots.

Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC-MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2ß-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.

Evaluation of anti-inflammatory, analgesic and TNF-α inhibition (upon RAW 264.7 cell line) followed by the selection of extract (leaf and stem) with respect to potency to introduce anti-oral-ulcer model obtained from Olax psittacorum (Lam.) Vahl in addition to GC-MS illustration.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax psittacorum (Lam.) Vahl., belongs to family olacaceae claimed as an "Issan folk medicine" portray the ethnomedicinal value like curative property of infection in the urinary tract, analgesic, antipyretic, skin-ulcer, antianemic (bark) as well as food additives (leaves). Research articles have proven the presence of anti-swelling property, laxative action, and antiviral activity against poliovirus moreover, the antioxidant property too. AIM OF THE EXPERIMENT: Evaluation of antiulcer property (induced within the oral mucosa) of the extract selected amongst two extracts based upon better property towards the ability of anti-inflammatory and analgesia through the in-vivo model as well as the inhibitory property of TNF-α (cell line RAW264.7). To justify the presence of activity extracts were introduced for GC-MS investigation. MATERIALS AND METHODS: Methanolic extracts (leaf; LME and stem; SME) were collected through maceration and introduced to carrageenan-induced paw edema to evaluate the anti-inflammatory activity and formalin-induced as well as tail-flick in-vivo models to evaluate the analgesic property. Anti-oral ulcer property was analyzed through the acetic-acid induced in-vivo model. The cytotoxicity was performed on mouse macrophages and fibroblast cells to find a toxic concentration of test substances and to evaluate their modulatory effect of TNF-α inhibition property against LPS induced toxicity. RESULTS: As compared to diclofenac (100 mg/kg) only LME and SME 200 mg/kg dose group have insignificant (P < 0.05) difference and P-values are 0.99 and 0.88 respectively. From the overall outcome, it can be concluded that compared to the diclofenac (100 mg/kg) group from 4th hours onwards LME (200 mg/kg) group was able to sustain the inflammation so similar. According to statistical consideration, LME (200 mg/kg) dose has also shown better results in formalin-induced analgesia as well as tail-flick. Cytotoxicity (CTC50) concentrations of LME and SME are 419.60 ± 4.09 and 230.21 ± 0.79 µg/ml respectively on RAW264.7 cell line. According to CTC50 the highest concentration of LME and SME is 400 and 200 µg/ml respectively has chosen to evaluate percentage inhibition of TNF-α as compared to diclofenac sodium (25 µg/ml). 50% inhibition was achieved by LME as well as diclofenac i.e. 51.2 ± 2.6% and 50.3 ± 0.8% instead of SME i.e. 45.2 ± 1.7%. As compared to the negative group on DAY-4, LME 200 mg/kg/bw dose shown proper growth of epithelial or mucosal layer which reveals proper healing of the surface of the tongue with no sign of injury. GC-MS results also reveal that, LME and SME both have Cyclohexasiloxane, dodecamethyl; Hexadecanoic acid, methyl ester which are responsible for anti-inflammatory and analgesic activity but besides, LME has more 4 compounds responsible for activities these are methyl salicylate; phytol; ß-Sitosterol; 9,12,15-Octadecatrienoic acid,2,3-bis[(trimethylsilyl)oxy]propyl ester, (Z, Z, Z). CONCLUSION: The overall outcomes of the study encapsulate that LME extract with a dose of 200 mg/kg/bw will be a good choice to overcome the above-cited ailments. Further studies upon this plant are needed to establish its importance in the human society through quantitative isolation of the metabolites and their pharmacokinetic as well as pharmacodynamic evaluation to establish the proper pathway of action.

Ameliorative effect of Boesenbergin A, a chalcone isolated from Boesenbergia rotunda (Fingerroot) on oxidative stress and inflammation in ethanol-induced gastric ulcer in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Boesenbergia rotunda (L.) Mansf. Kulturpfl., previously known as Boesenbergia pandurata (Family: Zingiberaceae) is a ginger species, locally known as fingerroot. It is an integral part of Southeast Asian traditional medicine in alleviating many gastrointestinal disorders such as flatulence, carminative, stomach ache, dyspepsia, and peptic ulcer. AIM OF THE STUDY: Earlier we have investigated the cytoprotective effect of Boesenbergia rotunda extract. In the present study, we investigated the gastroprotection activity of Boesenbergin A (BA), a chalcone isolated from Boesenbergia rotunda extract in ethanol-induced ulcer model in rats. Besides, the contribution of anti-inflammatory and anti-oxidant ability of BA as probable mechanisms involved in the anti-ulcer activity, also been studied. MATERIALS AND METHODS: BA was orally administered in rats before ulcer induction with ethanol. The lesions of the gastric mucosa were evaluated macroscopically and histopathologically. The efficiency of BA in mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, and lipid peroxidation (MDA) level were studied. The involvement of the anti-inflammatory capacity of BA was analyzed by using the measurement of cytokines such as TNF-α and IL-6. Finally, the expression of biomarkers such as HSP 70 and iNOS was analyzed at the transcriptional and translational levels. RESULTS: We confirmed the protective capacity of BA via the reduction of ulcerated and haemorrhagic areas. It has induced the protection through lowering GSH, MDA and increased NP-SH level. The plasma NO levels were significantly less in BA treated rats. Both cytokines TNF-α and IL-6 were decreased together with elevated PGE2. Upregulation of HSP and downregulation of iNOS were determined in immunohistochemical and gene expression studies CONCLUSIONS: The current results suggest that the prophylactic effect found with BA is due to (i) boosting of gastric mucus production and suppression of inflammatory mediators, via pro-inflammatory cytokines and (ii) modulating the oxidative stress response. The usefulness of Boesenbergia rotunda in folk medicine in treating ulcers partially could be due to the presence of this chalcone.