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Ethnopharmacological Relevance: In Argentine traditional medicine it is recorded the use of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) leaves for treating various affections that compromise the intestinal normal functioning., Aim of the Study: The aim of this study was to assess the effect of J. rhombifolia leaves lyophilized aqueous extract on the intestinal function by means of in vivo and ex vivo experimental assays for determinate the antidiarrheal and antispasmodic capacity. Furthermore, was to evaluate its acute toxicity potential by oral and intraperitoneal administration of extract., Materials and Methods: The in vivo assays were conducted by the experimental techniques of intestinal transit in mice, intestinal fluid accumulation in rats and Castor oil-induced diarrhea in mice. In the ex vivo assays, isolated rat duodenum and ileum segments were used for to evaluate the antispasmodic activity through contractile concentration-response curves induced by Carbachol and CaCl 2 . The acute toxicity of the extract was also investigated by oral and intraperitoneal administration., Results: The extract intraperitoneal administration at the doses 125, 250 and 500 mg/kg, caused a marked reduction in the normal intestinal transit and in the number of diarrheal episodes in a dose-dependent manner. However, the extract did not produce significant changes in the intestinal fluid accumulation with any of the tested dose. The extract demonstrated a non-competitive inhibitory effect on the contractions of intestinal smooth muscle experimentally provoked by the spasmogenic agents Carbachol and CaCl2 in a dose-dependent manner (IC 50  = 10.57 ± 1.38 and 6.29 ± 1.54 mg extract/ml Tyrode solution in the isolated organ bath, respectively). ANOVA indicated a significative effect of treatment (p < 0.001)., Conclusions: The scientific evidence achieved based in the used experimental models allows us to indicate that J. rhombifolia leaves lyophilized aqueous extract manifest an antispasmodic activity on intestinal smooth muscle without observation of apparent toxicity symptoms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC 50 = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products.

The leaves of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) are utilized as anti-alcoholic in Argentine folk medicine. This study was designed to investigate the anti-alcohol properties in adolescent male Wistar rats (postnatal day 29; 83-105 g of weight). We utilized the "self-administration model", which ethanol was offered in the standard home-cage through two-bottle free-choice regimen between an ethanolic solution (20% in tap water, v/v) and tap water with unlimited access for 24h per day for 10 consecutive days. The results obtained show that repeated administration of J. rhombifolia lyophilized extract, markedly reduced ethanol voluntary intake on dose dependent bases. The magnitude in reduction of daily ethanol intake was approximately 29%, 44% and 68%, for the rat groups treated with 62.5, 125 and 250 mg/kg of extract, respectively. Ethanol preference (proportion of ethanol intake versus total fluid intake) was significantly reduced: 21.37% ± 0.79 (0 mg/kg); 15.83% ± 0.93 (62.5 mg/kg); 15.22% ± 1.30 (125 mg/kg) and 9.38% ± 0.57 (250 mg/kg). Daily food intake was significantly higher (p<0.05) in the group treated with 250 mg/kg of JRLE in comparison with vehicle-dose group; the reduction in ethanol intake was associated with a compensatory increase in food intake, probably because in the control group animals a part of the total caloric intake was supplied by ethanol. Treatment was very well tolerated by all animals and without apparent side-effects. These results contribute to the scientific validation of the antialcoholic indication of this botanic species in Argentine folk medicine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The leaves of Jodina rhombifolia (Hook. & Arn.) Reissek (SANTALACEAE) is utilized in Argentine folk medicine for the treatment of alcoholism., Aim of the Study: To evaluate the antialcoholic activity of Jodina rhombifolia lyophilized aqueous extract (JRLE) in male Wistar rats., Materials and Methods: Rats were housed individually in standard plastic cages with wood chip bedding. Throughout the duration of experiment, ethanol was offered in the standard home-cage; two-bottle free-choice regimen between an ethanolic solution (20% in tap water, v/v) and tap water with unlimited access for 24h per day for 10 consecutive days. Rats were administrated intragastrically twice daily (1 ml/200 g) for 10 consecutive days, with the control vehicle (distilled water) or one of the doses of JRLE (125, 250 and 500 mg/Kg weight). Body weight, ethanol, water and food intake were measured every day at the same hour during the 10 days of experimentation., Results: The reducing effect of JRLE on daily ethanol intake was evidenced from the first day of treatment and persisted throughout the entire treatment period. The treatment did not significantly affect daily water intake neither the body weight gain. Daily food intake was higher in rat groups treated with JRLE., Conclusion: The results obtained in the present preliminary study show that repeated administration of JRLE, markedly reduces ethanol voluntary intake in male Wistar rats. The reduction of consumption was of remarkable magnitude and stable during the treatment 10-days., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, was studied in mice small intestinal transit. Its mechanism was evaluated in the presence of several adrenergic and cholinergic antagonist drugs and one opioid antagonist. Docking of dehydroleucodine into the homology model of the α2-adrenergic receptor allowed us to analyze the structural basis of their interactions. The experiments showed that dehydroleucodine delayed intestinal transit. The docking of dehydroleucodine showed a unique binding site, equivalent to the binding site of carozolol in the β-adrenergic receptor. The results suggested that dehydroleucodine produced an inhibitory effect on intestinal transit. Its action could be mediated, at least in part, through the α2-adrenergic receptor.

Ethnopharmacological Relevance: The increasing resistance of Helicobacter pylori to antibiotics demands the search for novel compounds from plant based sources. Artemisia douglasiana Besser is widely used in Cuyo region (Argentina) as folk medicine for the treatment of gastric ailments., Aim of Study: Based on our previous studies that Artemisia douglasiana exert cytoprotective actions against ethanol-induced gastric mucosal injury we assayed the anti-Helicobacter pylori effect of the Artemisia douglasiana extract and its active compound, dehydroleucodine., Materials and Methods: The in vitro anti-bacterial activity of Artemisia douglasiana extract and its active compound, dehydroleucodine were determined against one standard strain and six clinical isolates of Helicobacter pylori by using the agar dilution methods., Results: The results showed that both dehydroleucodine and Artemisia douglasiana extract had activity against the microorganism with MICs between 1-8 and 60-120 mg/L, respectively., Conclusions: Artemisia douglasiana may be a useful alternative treatment strategy principally in eradication of metronidazole and clarithromycin-resistant strain.

Dehydroleucodine (DhL), a sesquiterpene lactone obtained from Artemisia douglasiana, was screened for antidiarrheal effects. DhL inhibited castor oil-induced diarrhea in mice by judged by a decrease in the number of wet faeces in the DhL-treatment groups. DhL significantly reduced intestinal transit in mice. Yohimbine and phentolamine counteracted the inhibitory effect of DhL. It is suggested that alpha2-adrenergic receptors mediate the effect of DhL in intestinal motility. DhL reduced also intraluminal accumulation of fluid. Thus, the antidiarrheal activity of DhL is possibly related, at least in part, to its inhibitory action against gastrointestinal motility and the inhibition of enteropooling property.

The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58-96% at a dose from 12.5 to 100mg/kg. These results appear to confirm that the presence of a non-hindered alpha,beta-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.

The gastric cytoprotective activity of several molecules containing an alpha,beta-unsaturated carbonyl system is reported. We attributed this gastroprotective activity to the presence of a non-hindered Michael acceptor in the molecules assayed and suggested that the mechanism of protection would involve, at least in part, a nucleophilic attack of the sulphydryl group of the gastric mucosa to the beta carbon of the Michael acceptors of the compounds assayed.

Dehydroleucodine (DhL), a sesquiterpene lactone (SQL) of the guaianolide type isolated from Artemisia douglasiana Besser, shows a pharmacological cytoprotective effect and significantly prevents the formation of gastric and duodenal lesions induced by various necrotising agents in rodents. The effects of DhL, on two models of experimental colitis were examined. Colitis was produced in male Wistar rats by rectal instillation of 5 and 10% acetic acid, following the methods of Eliakim et al. and Le Duc et al., respectively. In mice colitis was produced by rectal instillation of 0.1 ml of 2,4,6-trinitrobenzene sulphonic acid (5 mg in 50% ethanol) (TNB) as previously described by Chin et al. In this study, the administration of DhL 40 mg kg(-1)(1 h before the induction of colitis) significantly decreased mucosal damage. This effect was consistent in both models. The protection provided by DhL was accompanied by significant decreases in diarrhoea and colon weight; and histologically normal mucosa without ulceration and mucus production were observed. This study shows that both TNB and acetic acid colitis can be pharmacologically controlled by DhL. Our results suggest that the protective activity of DhL in experimental colitis is mediated, at least in part, through the increase of glycoprotein synthesis, anti-inflammatory effect and inhibition of COX-2 induction, and by inhibiting the degranulation of cells containing monoamines., (Copyright 1999 Academic Press.)

Previously we reported that dehydroleucodine (DhL), a sesquiterpene lactone, shows gastric and duodenal cytoprotective activity. The mechanism is not mediated by antiacid secretory action; DhL stimulated mucus production and indomethacin pretreatment reduced cytoprotective action. In the present study we demonstrated that the gastric cytoprotective effect is antagonized by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine. The inhibitory action of NG-nitro-L-arginine is reversed by L-arginine, but not D-arginine. The findings suggest that NO is involved in the gastroprotection induced by DhL.

Previously, we reported that dehydroleucodine (DhL), a sesquiterpene lactone, protected the gastric mucosa of rats from absolute ethanol-induced lesions in a dose-dependent fashion. The mechanism is not mediated by an antiacid secretory action and DhL stimulated mucous production. In the present study, we report the effect of DhL on the mucosal production of prostaglandin E (PGE) and the mucosal release of PGE2 in rats stomach. DhL in acute treatment does not modify these values decreased by previous treatment with indomethacin or absolute ethanol. However, DhL in subchronic treatment significantly enhanced the mucosal production of PGE and the mucosal release of PGE2. Also, indomethacin pretreatment resulted in a significant reduction of the cytoprotective action of DhL. These results indicate the participation of endogenous prostaglandins in DhL protection against ethanol damage. Moreover, we suggest that the gastric protective activity of DhL against ethanol induced gastric mucosal damage is mediated, at least in part, through PGE and PGE2 in subchronic treatment.

The cytoprotective activity of the isolated functional groups of several sesquiterpene lactones is reported. Among them the highest activity is shown by alpha-methylen-gamma-butyrolactone and 2-cyclopenten-1-one. The activity shown by those Michael acceptors with a beta carbon hindered by an alkyl substituent was always lower or almost null. A three-way mechanism of action is proposed: a) reduced glutathione synthesis, b) prostaglandin synthesis and c) mucosal glycoprotein synthesis.

The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.