The diuretic effect of betulinic acid obtained from the hexane fraction of branches of
Citharexylum myrianthum
Cham., Verbenaceae, was evaluated in rats. Male Wistar rats were used for the ...experiments, and the urine volume was recorded for 8 h and further analyzed. Betulinic acid showed an increased diuretic and natriuretic action when orally given to rats (1 mg/kg) without changing the urinary elimination of K
+
and Cl
−
. The non-selective cholinergic receptor antagonist, atropine, and the non-selective inhibitor of the cyclooxygenase enzyme indomethacin completely avoided betulinic acid-stimulated diuresis. In addition, indomethacin and atropine could preclude betulinic acid
-
induced natriuresis. While no rise in the volume of urine was detected when betulinic acid was provided in combination with hydrochlorothiazide or amiloride, K
+
excretion was considerably enhanced in the hydrochlorothiazide plus betulinic acid and diminished in the amiloride plus betulinic acid association. This study reveals the diuretic effect of the pentacyclic triterpene betulinic acid, an action possibly related to the activation of cholinergic receptors and prostaglandins generation.
Graphical Abstract
Although diuretics have been widely used to treat hypertension along with others cardiovascular and renal disorders, no scientific data have been recorded to support the diuretic properties of
Rubus ...rosaefolius
Sm. (Rosaceae), a plant popularly used in Brazil to treat hypertension. Male Wistar rats were orally treated with: vehicle; hydrochlorothiazide; aqueous (AERR) and methanolic (MERR) extracts; dichloromethane (DCM), hexane (HEX) and ethyl acetate (EA) fractions; and the isolated compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (TUA) and 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone (PMF). At the end of the experiment (after 8 or 24 h), urine volume and other urine or plasma parameters were measured. AERR and MERR, at 100 and 30 mg/kg, respectively, induced diuretic, natriuretic and kaliuretic effect. Additionally, the DCM and HEX, but not EA, at 10 mg/kg, also increased urine volume and Na
+
and K
+
excretion. Both active constituents, TUA and PMF, at doses of 1 and 3 mg/kg, showed an augmented diuretic and natriuretic index. While TUA revealed a kaliuretic action, PMF did not interfere with potassium excretion. The compounds increased urinary creatinine, but not urea, levels. TUA was able to decrease calcium excretion, as well as HCTZ, while PMF effect was associated with increased urinary prostaglandin E
2
levels. The non-selective muscarinic receptor antagonist (atropine) prevented TUA-induced diuresis. In addition, indomethacin (a cyclooxygenase inhibitor) and atropine, exhibited the ability to block the diuretic effects prompted by PMF. Our study demonstrates the diuretic effect of extracts, fractions and two natural compounds obtained from
R. rosaefolius
leaves in rats.
Garcinia humilis
is popularly used to treat digestive, intestinal and inflammatory illness. We investigated the in vivo and in vitro effects of the methanol extract of
G. humilis
leaves (MEGh) on ...inflammatory cells behavior (migration and chemical mediators release) and hypersensitivity. Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice treated orally with MEGh (0.1–30 mg/kg). Leucocyte migration, chemical mediators secretion (TNF, IL-1β, IL-6 and CXCL1) and protein exudation were quantified in the exudate. The adhesion molecules expression (CD62L and CD18), chemical mediators and chemotaxis was evaluated using neutrophils or macrophages RAW.264.7 previously treated with the extract (1–100 µg/mL) and activated with LPS. The anti-inflammatory activity of the isolated compounds friedelin, canophyllol, amentoflavone and 3-desmethyl-2-geranyl-4-prenylbellidypholine xanthone (10 μM) was evaluated in macrophages nitric oxide (NO) and TNF release. MEGh, given orally (30 mg/kg), significantly reduced neutrophil migration and decreased TNF, IL-1β and CXCL1 levels, without interfering with protein exudation and IL-6. In vitro, the extract significantly reduced IL-1β and IL-6 levels but did not alter TNF and CXCL1. The MEGh also reduced the expression of CD62L and CD18 and consequently neutrophil chemotaxis. The compounds friedelin, amentoflavone and 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone decreased the secretion of NO and TNF by RAW264.7. The MEGh effects were extended to the pain-like behaviour induced by carrageenan in the mice hindpaw. MEGh presented important anti-inflammatory effects probably due to its activity on neutrophil migration and on important chemical mediator release, scientifically reinforcing its use as medicinal plant.
Gastroprotection and mechanism of action of methanol extract and canthin-6-one from Simaba ferruginea A. St-Hil. in ethanol and indomethacin ulcer models.
Simaba ferruginea A. St-Hil. (Simaroubaceae) ...is a subshrub typical of the Brazilian Cerrado, whose rhizomes are popularly used as infusion or decoction for the treatment of gastric ulcers, diarrhea and fever.
To evaluate the pharmacological mechanism(s) of action of the antiulcer effects of the methanol extract of Simaba ferruginea and its alkaloid canthin-6-one.
Rhizome of Simaba ferruginea was macerated with methanol to obtain the methanol extract (MESf) from which was obtained, the chloroform fraction. Canthin-6-one alkaloid (Cant) was purified and then isolated from the chloroform fraction (CFSf). The isolated Cant was identified by HPLC. Anti-ulcer assays were determined using ethanol and indomethacin-induced ulcer models in mice and rats respectively. In order to determine the probable mechanisms of actions of MESf and Cant animals were pretreated with l-NAME prior to anti-ulcer agent treatments and ulcer induction and nitric oxide (NO) level determined in order to assess NO involvement in the gastroprotective effects. Assays of malondialdehyde (MDA), myeloperoxidase (MPO), pro-inflammatory cytokines: interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2) were also carried out according to previously described methods.
The results indicate that the antiulcerogenic effects of MESf and Cant in ethanol-induced ulcer is mediated in part through increase in the production of protective endogenous NO as the antiulcerogenic activity of MESf and Cant was reduced in animals pre-treated with l-NAME. In indomethacin-induced ulcer pre-treatment with MESf and Cant showed reduction in the levels of MPO and MDA in the gastric tissue, thus indicating the participation of the antioxidant mechanisms on the gastroprotective effects. The plasma levels of IL-8 in ulcerated rats with indomethacin were also reduced by Cant, but not by MESf, indicating that inhibition of this cytokine contributes to the gastroprotective effect of Cant. However MESf and Cant had no effect on the mucosal membrane levels of PGE2, indicating that the gastroprotective effects of these agents is independent of PGE2 modulation.
The results obtained in this study with MESf and Cant added insights into the pharmacological mechanisms involved in their mode of antiulcer action. The results indicate that Cant is one of the compounds responsible for these effects. Such findings are of extreme importance in the strive for future development of potent, safer and effective antiulcer agent. The efficacy of MESf and Cant in gastroprotection shows that Simaba ferruginea might be a promising antiulcer herbal medicine, in addition to confirming the popular use of this plant against gastric ulcer models utilised in this study.
Display omitted
•This study shows the diuretic and saluretic actions of (-)-epicatechin (EPI) in rats.•The combination with HCTZ strengthened EPI-induced diuresis.•The treatment with amiloride plus ...EPI preserved the potassium-sparing effect.•EPI-induced diuresis was precluded in the presence of a cyclooxygenase inhibitor.
Several studies have suggested that (-)-epicatechin-containing foods and plant extracts benefit conditions that affect the cardiovascular system, such as hypertension and endothelial dysfunction. However, no study was conducted so far to evaluate the potential of this flavonoid on diuretic activity assay. For that, female Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with (-)-epicatechin (EPI), hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of EPI in combination with diuretics for clinical use, as well as with L-NAME, atropine and indomethacin were also explored. Cumulative urine volume, plasma and urinary parameters were evaluated at the end of 8 h experiment. When given to NTR and SHR, at doses of 0.3, 1 and 3 mg/kg, EPI was able to stimulate both diuresis and saluresis (Na+, K+ and Cl−), without interfering with plasma electrolyte content or urinary pH and uric acid values, when compared with VEH-treated only rats. The combination with HCTZ, but not with furosemide or amiloride, successfully strengthened EPI-induced diuresis. This effect was not accompanied by a potentiation of the saluretic effects. On the other hand, when given EPI in combination with amiloride, a significant increase in Cl− excretion and maintenance of the potassium-sparing effects characteristic of this class of diuretics were detected. In addition, the diuretic effect of EPI was enhanced after pretreatment with L-NAME and its action was significantly precluded in the presence of indomethacin, a cyclooxygenase inhibitor. In conclusion, this study shows the diuretic and saluretic properties of EPI in rats, adding another biological activity whose effect may contribute to the different positive actions already described.
Velutinol A is a pregnane compound isolated from the rhizomes of the Brazilian plant
Mandevilla velutina that interferes with kinin actions and possesses anti-inflammatory action. Here, we ...investigate the effect produced by velutinol A in different models of inflammatory nociception. The nociceptive effect caused by the intraplantar injection of phorbol myristate acetate (PMA, 50 pmol/paw) in mice was practically abolished by coadministration of velutinol A (1–10
nmol/paw). In contrast, the coadministration of velutinol A (10
nmol/paw) failed to affect the nociceptive response elicited by either bradykinin (BK, 10
nmol/paw) or prostaglandin E
2 (PGE
2, 10
nmol/paw). Of note, velutinol A (10
nmol/paw) partially inhibited the nociceptive response caused by capsaicin (1
nmol/paw). However, velutinol A (10
μM) did not significantly interfere with the specific binding sites of
3Hresiniferatoxin or
3HBK in vitro. Our data also suggest that these effects are related with its ability to interact with kinin B
1 receptor-mediated mechanisms, as the cotreatment of mice with velutinol A (10
nmol/paw) consistently blocked the nociceptive response induced by the selective B
1 receptor agonist des-Arg
9-BK. Finally, the persistent hyperalgesia produced by intraplantar injection of carrageenan (300
μg/paw) was completely reversed by the coadministration of velutinol A (10
nmol/paw). Collectively, the present results show that the pregnane compound velutinol A produces peripheral antinociceptive action in some models of acute and persistent inflammatory pain by interacting with kinin B
1-receptor mediated effects. Thus, velutinol A or its derivatives could constitute an attractive molecule of interest for the development of new analgesic drugs. Additional studies are now in progress in order to further explore its precise mechanism of action on B
1 receptor pathways.
The previous study showed that 1,5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) obtained from Garcinia achachairu Rusby (Clusiaceae) branches induces acute ...diuresis in normotensive (NTR) and spontaneously hypertensive rats (SHR) after 8 h of the experiment. In complementarity, the present study evaluated the prolonged diuretic and renoprotective effects of TDP in both NTR and SHR. The animals received, once a day, oral treatment with TDP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (VEH; 10 mL/kg). At the end of 7 days, the urine, blood, and kidney samples were collected for biochemical and histological analyzes. The urinary volume of both NTR and SHR after 7 days of treatment with the TDP was significantly increased, associated with augmented urinary electrolyte excretion levels. The treatments did not modify the urinary pH values nor the parameters analyzed in plasma (Na+, K+, Cl−, and Ca2+). Concerning the renal analyzes, when compared with the VEH-treated NTR group, while the activity of the enzymes catalase (CAT) and N-acetyl-β-D-glucosaminidase (NAG), as well as nitrite levels, were increased, the generation of lipid hydroperoxides and the activity of the enzyme myeloperoxidase (MPO) were unaltered. On the other hand, the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of reduced glutathione (GSH) in kidney homogenates of the SHR group were decreased. However, TDP augmented the levels of GSH and GST activities and reduced the levels of nitrite and the activities of CAT and MPO, when compared with VEH-treated only SHR. Besides, the treatment with TDP alleviated the morphological changes of the renal corpuscle region of SHR. Together, these results revealed the prolonged diuretic effect of TDP and their renal protective effect by improving the antioxidative capacity.
In addition to the known cilistol A, two new withanolides have been isolated from leaves and stem of Solanum sisymbiifolium, and assigned the structures 1-oxo-5,6; 22,26; ...24,25-triepoxy-17,26-dihydroxyergost-2-ene and 1-oxo-22,26; 24,25-diepoxy-5,6,17,26-tetrahydroxy ergost-2-ene, namely cilistepoxide and cilistadiol.
The present work describes the evaluation of the antidepressant-like activity of the extract, fractions, and compounds obtained from the aerial parts of
Solanum capsicoides
. The methanolic extract ...(MESC) obtained by conventional maceration was partitioned with solvents of increasing polarities yielding the respective fractions of hexane (HE), dichloromethane (DCM), and ethyl acetate (EA). The dichloromethane and ethyl acetate fractions were submitted to chromatographic and spectroscopic techniques, leading to the isolation and identification of cilistadiol (
1
), astragalin (
2
), and cilistol A (
3
). In relation to the antidepressant activity, the extract was active against the forced swimming test (FST) at a concentration of 300 mg/kg an ED
50
(deffective dose that reduces 50% of immobility time) of 120.3 (117.3–123.4) mg/kg. Similar values were observed when evaluated in the tail suspension test (TST). In addition, the results showed no influence on motor behavior when evaluated in the open field test (OFT). Based on the observed profile of the MESC, dichloromethane fraction presenting the best profile, in both FST and TST test. Likewise, the fraction also did not present motor impairment when evaluated by the OFT test. Considering that the dichloromethane fraction was more effective, the isolated compounds cilistadiol and cilistol A were evaluated in the same experimental models. In FST, both compounds had a significant antidepressant-like effect, with ED
50
values of 0.22 (0.16–0.28) and 1.03 (0.89–1.18) μmol/kg, respectively. When evaluated in the TST, showed ED
50
values of 0.30 (0.18–0.52) and 1.49 (1.27–1.73) μmol/kg, respectively. The isolated compounds also did not present significant differences in the motor behavior when evaluated on OFT test in comparison with the control group. No toxicological parameters were observed until the highest dose of MESC (2000 mg/kg), demonstrating safety in the use of this plant.
The present study was designed to investigate the gastroprotective effect of xanthones 7-preniljacareubin (PJB), 1,3,5,6-tetrahydroxy xanthone (THX), 3-demethyl-2-geranyl-4-prenylbellidypholine (DGP) ...and 1,5,8-trihydroxy-4′, 5′-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) isolated of branches from G. achachairu. Their structures were identified through the spectroscopic analysis in comparison with previously reported data. The xanthones were tested at dose of 10 mg/kg against ethanol 60%/HCl 0.3 N-induced gastric ulcer in female swiss mice. The xanthones PJB, THX, DGP and TDP exhibit gastroprotective effect after intraperitoneal treatment, but only the first two displayed anti-ulcer activity after oral administration. Both PJB and THX augmented the antioxidative capacity of tissue by an increase in glutathione levels, as well as were able to prevent an increase in myeloperoxidase activity and tumor necrosis factor level. On the other hand, only THX showed an in vitro free radical scavenger activity, and only PJB avoided mucus depletion on gastric mucosa, which was not associated with an increase in mucin production at glandular level. In addition, PJB and THX inhibited the in vitro H+K+-ATPase activity at similar range as omeprazole. Together, these results demonstrate the anti-ulcer efficacy of xanthones isolated from G. achachairu, which can contribute for future directions in the development of effective strategies to improve gastric diseases.
Display omitted
•Xanthones isolated from Garcinia achachairu display gastroprotective activity.•Anti-ulcer effect is due the ability of increase protective factors of gastric mucosa.•H+,K+-ATPase activity inhibition can explain xanthones anti-secretory effect.•Efficacy of xanthones can contribute to improve the management of gastric diseases.
PDF
