Actions of Ya-hom, a herbal drug combination, on isolated rat aortic ring and atrial contractions.

The effect of the Thai popular medicine Ya-hom on cardiovascular function was studied in isolated rat aortic ring and atrium by comparison with norepinephrine (NE). Water extraction of Ya-hom at concentrations of 0.83, 1.67, 8.33 and 16.67 mg/ml stimulated aortic ring contraction dose-dependently. The maximum contraction, at 16.67 mg/ml, was about 14% that of NE. This stimulatory effect of Ya-hom was inhibited partially by phentolamine, which indicated that the effect of Ya-hom was partially dependent on the alpha receptor, similar to NE. Administration of Ya-hom with NR decreased the force of aortic ring contraction as compared to the effect of NE alone, indicating that Ya-hom may have a partial alpha-agonist activity. Ya-hom at concentrations of 1.67, 8.33 and 16.67 mg/ml showed a dose-dependent, positive inotropic and negative chronotropic effects. Ya-hom increased the force of isolated atrial contraction with a slow onset and prolonged action. In contrast to norephinephrine, which acted on beta1 receptor, causing positive inotropic and chronotropic effects, propranolol did not alter the effect of Ya-hom on the atrial contraction. This shows that the action of Ya-hom on atrial contraction does not involve beta receptor.

Effects of Ya-hom on blood pressure in rats.

The effects of Ya-hom, a traditional Thai herbal formulation, on blood pressure were evaluated to verify its use for fainting treatment. Ya-hom has several recipes, which are composed of different medicinal plants in varying ratio. We have selected the most popular commercial preparation to determine the effect on the blood pressure in rats. The water extract of Ya-hom at doses of 0.2, 0.4, 0.6 and 0.8 g/kg initially transiently decreased pressure and over time, increased blood pressure. The duration of the Ya-hom effect on decreasing and increasing blood pressure was dose dependent. The time to maximal effect of Ya-hom on increasing blood pressure was also dose dependent. Phentolamine attenuated the blood pressure decreasing effect but did not affect the blood pressure increasing effect of Ya-hom. Ya-hom was previously shown to increase aortic ring contraction, which was partially inhibited by phentolamine, and increased atrial contraction. It is possible that phentolamine inhibits the effect of Ya-hom on vascular smooth muscle contraction resulting in a prominent positive inotropic effect. This may be the same reason that phentolamine does not influence the effect of Ya-hom on increasing blood pressure. The dominant effect of Ya-hom on increasing blood pressure supports the use of Ya-hom for the treatment of fainting.

Effects of Ya-hom on the gastric secretion in rats.

The effects of Ya-hom, Thai traditional recipe, on gastric-secretory function was evaluated to verify its use for stomach discomfort treatment. The actions of Ya-hom on the gastric acid, pepsin and mucus secretions were studied in histamine- and carbachol-induced gastric fistula rats. After the first hour of collection, histamine (10 mg/kg, intramuscular injection) or carbachol (20 microg/kg, intravenous injection) were injected to stimulate gastric secretion, and water or redissolved lyophilized Ya-hom extract (0.5, 1, 2 and 4 g/kg) were intraduodenally injected. The gastric samples were collected every hour for 5 h, at the end of which, the glandular part of the stomach was assayed for the visible mucus content. Ya-hom inhibited both histamine- and carbachol-induced gastric acid, pepsin and soluble mucus secretions in a dose-dependent manner. Ya-hom had a lower maximum inhibition on the acid-stimulating effects of the histamine than that of carbachol. Ya-hom had higher maximum inhibition on the pepsin and soluble mucus-stimulating effects of histamine than that of carbachol. Ya-hom also had a higher elevated effect on histamine-induced visible mucus than that of carbachol. This study reveals that Ya-hom inhibits the stimulatory effects of histamine and carbachol on the acid, pepsin and soluble mucus secretion but potentiates the visible mucus secretion. Attenuating gastric secretion by secretagogues and increasing gastric barrier effects are parts of Ya-hom's action on stomach discomfort treatment.

Effects of Aloe preparation on the histamine-induced gastric secretion in rats.

The effects of Aloe preparation containing 80% Aloe gel on the gastric acid, pepsin and mucus secretion were evaluated in histamine-induced gastric fistula model in rats by comparison to the effects of placebo and fresh Aloe gel. Aloe preparation and placebo at a dose of 8 ml/kg inhibited gastric acid but stimulated pepsin secretory rates. On the other hand, fresh Aloe gel at a dose of 6.4 ml/kg prolonged histamine stimulatory effects on the gastric acid secretion while it inhibited gastric pepsin secretion. Both Aloe preparation and placebo increased soluble mucus secretory rate in a dose-dependent manner whereas fresh Aloe gel had no effect. The Aloe preparation and placebo at a dose of 8 ml/kg increased the gastric visible mucus content while fresh Aloe gel slightly increased the visible mucus content. This study reveals that fresh Aloe gel prolonged the effects of histamine-stimulated acid secretion and inhibits pepsin secretion in histamine-treated rats. The Aloe preparation inhibited gastric acid, stimulated pepsin and mucus secretion. However, there were no difference in the secretory rates of Aloe preparation and placebo-treated rats at the same doses. This result indicates that the observed effects of Aloe preparation was mostly due to other compositions of the preparation rather than Aloe gel itself. Since the highest dose of Aloe gel preparation used in the present study was limited by the volume of the instilled solution in gastric fistula model, the effects of Aloe vera gel were not able to be observed in the present study might be due to the inadequate dose of the preparation.

Guava leaf extract and topical haemostasis.

The effects of guava leaf extract on the bleeding time and the three main mechanisms of haemostasis: vasoconstriction, platelet aggregation and blood coagulation, were investigated. The water extract of guava leaves did not shorten bleeding times in rats. Guava leaf extract potentiated the vascular muscle contraction induced in rabbits by phenylephrine, and when given alone it stimulated human platelet aggregation in vitro in a dose-dependent manner. On the other hand, it significantly prolonged blood coagulation; activated partial thromboplastin time (APTT) test (p < 0.05). The higher the concentration of the extract, the longer APTT was observed. Thus, a water extract of guava leaves showed ambiguous effects on the haemostatic system. Guava leaf extract did not affect bleeding times, it stimulated vasoconstriction and platelet aggregation but it inhibited blood coagulation. Therefore, guava leaf extract is not recommended as a haemostatic agent.

Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants.

A number of Thai medicinal plants, recommended as remedies for herpesvirus infection and have been used in primary health care were investigated for their intracellular activities against herpes simplex viruses (HSV). Centella asiatica L., Maclura cochinchinensis Cornor, and Mangifera indica L. contained both anti-HSV-1 and -2 activities, as determined by plaque inhibition assay. An inhibition of the production of infectious HSV-2 virions from infected Vero cells could also be demonstrated. Combinations of each of these reconstituted extracts with 9-(2-hydroxyethoxymethyl) guanosine (acyclovir; ACV) resulted either in subadditive, additive, or synergistic interaction, against HSV-2, depending on the dose of ACV used; mixture of C. asiatica and M. indica exerted an additive effect in a similar assay. Furthermore, the inhibitory effects of these plant extracts were also substantiated by flow cytometric analysis of virus-specific antigens in the infected cells. The active constituent present in C. asiatica extract was determined to be asiaticoside while in M. indica was mangiferin. Thus, these data suggest therapeutic potential of these plant extracts.

Anti-herpes simplex virus component isolated from Maclura cochinchinensis.

The powerful anti-herpes simplex virus (HSV) activity of Maclura cochinchinensis in vitro prompted us to carry out biologically-guided separation of the active component(s). Ethyl acetate and methanol extracts exhibited anti-HSV-2 activity at EC50 values of 38.5 micrograms/ml and 50.8 micrograms/ml, respectively. Although petroleum ether extract was inactive, a chloroform extract was too toxic to the test cell culture to perform the test. Biologically-guided chromatographic separation of the ethyl acetate extract yielded compound A, identified as morin using a spectroscopic method. Morin exhibited anti-HSV-2 activity at an EC50 value of 53.5 micrograms/ml. Morin pentaacetate was synthetized, but was inactive. This result suggested that free hydroxyl groups are required for anti-HSV-activity, as demonstrated previously for the antiviral activity of other flavonoids.

The efficacy of Aloe vera cream in the treatment of first, second and third degree burns in mice.

Aloe vera has been recognized as a valuable medicinal plant for the treatment of burns. Extensive studies have described its antiinflammatory, wound healing and related activities, but the instability of aloe gel confuses pharmacological data, leads to inconsistency in treatments and inconvenience in daily preparation. These obstacles prompted us to develop a stable aloe preparation, aloe cream, that we tested on artificial thermal burns in mice. Aloe cream when applied immediately to first degree burns delayed progressive damage and accelerated the healing rate more effectively than fresh aloe gel. Both aloe cream and fresh aloe gel prevented further skin damage and casting of dead epidermis was less than in control. For second degree burns the healing rate was enhanced by aloe cream and fresh aloe gel: less inflammation was observed in areas treated with either of these than in untreated areas or those treated with the cream base. For third degree burns the efficacy of aloe cream and fresh aloe gel could not be evaluated statistically because of infection. It was observed that aloe cream enhanced epithelialization but failed to show antiinflammatory activity. No differences in epithelialization and inflammation were observed among mice treated with fresh aloe gel, cream base or control. All these findings confirm that Aloe vera gel is effective for burn treatment if it is well preserved.

Antidiabetic activity of Aloe vera L. juice. I. Clinical trial in new cases of diabetes mellitus.

Aloe vera gel has been claimed to have antidiabetic activity but not all published results are consistent. We investigated the effect of oral administration of one tablespoonful of Aloe vera juice, twice a day for at least 2 weeks in patients with diabetes. Blood sugar and triglyceride levels in the treated group fell; cholesterol levels were not affected. The results suggest the potential of aloe vera juice for use as an antidiabetic agent.

Antidiabetic activity of Aloe vera L. juice II. Clinical trial in diabetes mellitus patients in combination with glibenclamide.

The effect of Aloe vera juice in combination with glibenclamide was investigated in diabetic patients. There was no response to glibenclamide alone but Aloe vera juice significantly reduced levels of fasting blood glucose within two weeks and of triglycerides within four weeks. It showed no effect on cholesterol levels and had no toxic effects on kidney or liver function as assessed by blood chemistry. The results support the use of Aloe vera in the treatment of diabetes.

Mosquito repellent activities of ocimum volatile oils.

Essential oils obtained from Ocimum americanum, O. basilicum, O. basilicum fa. citratum, O. gratissimum and O. tenuiflorum, were tested for mosquito repellent and larvicidal activities. All the oils exhibited both activities. O. basilicum showed the strongest larvicidal activity (EC(50) = 81, EC(90) = 113 ppm), while O. gratissimum exhibited the longest duration of action for mosquito repellent activity (more than two hours). Gas chromatographic analysis indicated the presence of camphor, caryophyllene oxide, cineole, methyleugenol, limonene, myrcene, and thymol, all known insect repellents.

Mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L.

Studies of the mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. (Bignoniaceae), were performed using the liquid preincubation method of the Salmonella/microsome test. At the highest dose tested, 100 micrograms/plate, both compounds showed no mutagenicity and no cytotoxicity toward S. typhimurium strains TA98 and TA100 either in the presence or absence of S9 mix. However, these substances were antimutagens toward 2-aminoanthracene, aflatoxin B1 (in TA98), and dimethylnitrosamine (in TA100); but neither substance inhibited the direct mutagenic activity of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide nor that of sodium azide in strains TA98 and TA100, respectively.

Randomized controlled trial of Cassia alata Linn. for constipation.

Cassia alata Linn. is a medical plant. Its leaves have been claimed to be effective as a laxative. The studies done so far have shown no toxicity as a result of consuming Cassia alata Linn. leaves. The plant has been found to contain anthraquinones, presumed to be the active ingredient causing the laxative effect. The objective of the study was to test efficacy of Cassia alata Linn. leaves for treatment of constipation compared with a placebo and mist. alba in a multicenter randomized controlled trial carried out in one provincial and 5 community hospitals. Eighty adult patients admitted to 5 community hospitals and one provincial hospital with at least 72 hours of constipation were included in the study. Twenty-eight patients were in the placebo group, 28 in the mist. alba group, and 24 in Cassia alata Linn. group. Each patient was given 120 ml of fluid with caramel color, mist. alba, or Cassia alata Linn. infusion at bed time. Evaluation was performed after 24 hours whether the patient defecated or not. The characteristics of the patients among the three groups were not different. Eighteen per cent of patients in the placebo group passed stools within 24 hours, whereas, 86 and 83 per cent of patients in mist. alba and Cassia alata Linn. groups respectively, passed stools. The differences observed between placebo and mist. alba, placebo and Cassia alata Linn. were statistically highly significant, P less than 0.001 and clinically important. Minimal self-limited side effects, i.e., nausea, dyspepsia, abdominal pain and diarrhea were noted in 16-25 per cent of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized double blind study of Curcuma domestica Val. for dyspepsia.

Curcuma domestica Val. is a medicinal plant. It has been claimed to be effective for dyspepsia. The studies done so far showed no toxicity due to consuming Curcuma domestica Val. The plant has been found to contain volatile oil and curcuminoids which are believed to be the active ingredients. The objective of the study was to test the efficacy of Curcuma domestica Val. rhizome for treatment of dyspepsia compared with a placebo and flatulence in a multicenter, randomized, double-blind trial carried out in one provincial and 5 community hospitals. One hundred and sixteen adult patients who had acid dyspepsia, flatulent dyspepsia, or atonic dyspepsia were included in the study. Forty-one (41) patients were in the placebo group, 36 and 39 were in the flatulence and Curcuma domestica Val. groups respectively. Each patient received 2 capsules of placebo or study drugs 4 times a day for 7 days. Each patient was then assessed for symptoms response, side effects and satisfaction. Ten patients did not participate in the follow-up. The baseline characteristics of the patients among the three groups were not significantly different. Fifty-three (53) per cent of the patients receiving placebo responded to the treatment whereas 83 per cent of the patients receiving flatulence and 87 per cent of patients receiving Curcuma domestica Val. responded to the treatment. The differences in efficacy between placebo and active drugs were statistically significant and clinically important. Mild and self-limited side effects were observed at similar frequency in the three groups. About 50 per cent of the patients in each group were satisfied with the treatment they received.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on Aristolochia III. Isolation and biological evaluation of constituents of Aristolochia indica roots for fertility-regulating activity.

An ethanol extract of Aristolochia indica roots decreased fertility in both rats and hamsters when administered postcoitally (days 1-10 and 1-6, respectively). Petroleum ether (A), CHCl3 (B), and aqueous (C) fractions, tested similarly in rats, were inactive and/or toxic. Partition of fraction B afforded non-acidic (D) and acidic (E) fractions. Savinin (1), isolated from fraction D and not previously reported from the Aristolochiaceae , was inactive when administered postcoitally to rats. Aristolochic acid-I (2), reported previously from A. indica and isolated from fraction E, was inactive when administered postcoitally to rats and toxic when administered postcoitally to hamsters. (12S)-7,12- Secoishwaran -12-ol (3), previously reported from A. indica and isolated from fraction A, did not interrupt pregnancy when administered to mice on day 6 of pregnancy. Four additional compounds, aristolic acid (4) [prepared from aristolochic acid-I (2)], methyl aristolate (5) [prepared by methylating aristolic acid (4)], and cis- and trans-p-coumaric acid (both oblate commercially), were similarly tested in mice and found to be inactive. Aristolic acid (4), and the cis- and trans-p-coumaric acids also were inactive when administered postcoitally (days 1-10) to rats. Seven compounds reported previously from A. indica were also isolated, as were a new naphthoquinone, aristolindiquinone (6) (fraction E), and magnoflorine (fraction C).

Effect of (+)-gossypol on fertility in male hamsters.

(+)-Gossypol was isolated from the bark of Thespesia populnea and tested for its ability to inhibit the fertility of male hamsters. Male hamsters of proven fertility were treated orally for 54 days with 40 mg/kg of (+)-gossypol, 40 mg/kg of racemic gossypol, or 5% gum acacia (vehicle control) and were mated with estrous female hamsters during the fourth and seventh weeks of treatment. Both the control and the (+)-gossypol-treated animals exhibited normal fertility throughout the experiment. The racemic gossypol-treated animals were infertile when evaluated during both the fourth and seventh weeks of treatment. Morphologic examination of the testicular tissue could not explain the loss of fertility. These data demonstrate the inability of (+)gossypol to decrease male fertility and suggest that the activity of racemic gossypol may be due primarily to the presence of the (-) optical isomer.