Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human.

Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of andrographolide (AND) in the blood plasma of rats and human volunteers following the oral administration of Andrographis paniculata extract (APE) and Andrographis paniculata fixed combination Kan Jang tablets were developed and used for the pharmacokinetic study. Andrographolide was quickly and almost completely absorbed into the blood following the oral administration of APE at a dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND is bound to plasma proteins and only a limited amount can enter the cells, the pharmacokinetics of AND are described well by a one-compartment model. Renal excretion is not the main route for eliminating AND. It is most likely intensely and dose dependently metabolized. Following the oral administration of four Kan Jang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans, maximum plasma levels of approximately 393 ng/ml (approx. 1.12 microM) were reached after 1.5-2 hours, as quantified using a UV diode-array detection method. Half-life and mean residence times were 6.6 and 10.0 hours, respectively. AND pharmacokinetics in humans are explained well by an open two-compartment model. The calculated steady state plasma concentration of AND for multiple doses of Kan Jang (after the normal therapeutic dose regimen, 3 x 4 tablets/day, about 1 mg AND/kg body wt./day) was approximately 660 ng/ml (approx. 1.9 microM), enough to reveal any anti-PAF effect, particularly after drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx. 3.8 microM, while for anti-PAF effect EC50 - 5 microM).     

Efficacy of Sambiloto Extracts,Andrographis paniculate, (Burm. F) in Inhibiting Diabetic Retinopathy Progression: An in Vivo Study

Background:Diabetic retinopathy (DR) is one of diabetes mellitus complication and occurred in retinal microvascular. This study was aimed to investigate the efficacy of Sambiloto, Andrographis paniculate (A. paniculata) extract on glycemic profile, antioxidant and inflammatory cytokine parameters in diabetic rats, and phytochemical analysis of A. paniculata. Methods:A. paniculata extract (APE) was carried out by maceration with ethanol. Diabetes mellitus in Wistar male rats was induced with streptozotocin. Retinal vessel diameters were estimated using a method by Vucetic. Inflammatory cytokine and antioxidant parameters were evaluated in retinal tissue. The alkaloid and flavonoid contents in extract were analyzed using thin layer chromatography method. Results:Funduscopic examination presented some changes in the diameter of the blood vessels. The vessel diameter in the diabetic retinopathy group with APE in concentration of 100 and 200 mg/kg BW groups was significantly lower than in the DR group (p<0.05). The administration of APE in dosages of 100 and 200 mg/kg BW showed reduced glutathione, SOD, and catalase levels compared to the DR group (p<0.05).Conclusion:A. paniculata extract doses of 100 and 200 mg/kg BW improved diabetic retinopathy in rats through hypoglycemic effects, antioxidant effects, and anti-inflammatory mechanisms.Key Words: Andrographis paniculata, Antioxidants, Diabetic Retinopathy, Plant Extracts, Retinal Vessels     

Effects of Andrographis paniculata (Burm. F.) Extract on Diabetic Nephropathy in Rats

Background:Hyperglycemia and accumulation of advanced glycation end products (AGEs) play a significant role in the development of diabetic nephropathy. Andrographis paniculata (AP) is a plant with high flavonoid content with the potential to suppress oxidative stress activity in cells and tissue. This study was aimed to investigate the role of Andrographis paniculata extract (APE) in protecting kidney damage due to the formation of AGEs in the renal glomerulus in diabetic rats.Methods:A total of 30 male Sprague Dawley rats were randomly divided into five groups as follows: normal control group, streptozocin (STZ) induced diabetic group, STZ-induced diabetic group with AP extract (100 mg/kg BW), STZ-induced diabetic rats with AP extract (200 mg/kg BW), and STZ-induced diabetic rats with APE (400 mg/ kg BW). Blood glucose levels were measured before treatment and after treatment. Serum and urine parameters were determined. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination.Results:The finding of this study showed that treatment APE at the dose of 200 mg/kg and 400 mg/kg ameliorated kidney hypertrophy index. SOD, catalase, and GSH activities significantly decreased in the kidney of STZ-diabetic rats compared to the normal control rats. Treatment with APE significantly decreased malondialdehyde level at the dose of 200 and 400 mg/kg BW.Conclusion:This study revealed evidence for improving diabetic retinopathy in male rats treated with Andrographis paniculata extract. APE significantly decreased oxidative stress activities in kidney of diabetic rats.Key Words: Andrographis, Diabetic Nephropathies, Streptozocin, Rats, Oxidative Stress     

Antiulcer activity of Andrographis paniculata (Burm.f.) wall. against cysteamine-induced duodenal ulcer in rats

Antiulcer activity of Andrographis paniculata was evaluated by cysteamine induced duodenal ulcer model in rats. Male albino Wistar rats were pre-administered with 200 mg/kg body wt. of hydroalcoholic extact of Andrographis paniculata (HAEAP) orally, for 30 days prior to i.p. administration of 420 mg/kg body wt. of cysteamine as a single dose. Rats preadministered with 30 mg/kg body wt. of ranitidine served as standard drug. Ulcer index, thiobarbituric acid reactive substances, mucin, glutathione peroxidase and myeloperoxidase activities, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, glycoproteins and membrane bound enzyme activities were measured in duodenum of experimental animals. The ulcer score and myeloperoxidase activity were significantly minimized in rats treated with HAEAP. Mucin content was found to be preserved in rats treated with the extract. GSH/GSSG ratio and glutathione peroxidase activities were found to be maintained by the HAEAP. Level of lipid peroxidation products was found to be significantly low in HAEAP treated rats compared to ulcer control rats. The basolateral and brush border membrane bound enzyme activities which were depleted significantly in ulcer control rats were found to be maintained in rats pre-treated with the extract. The ulcer preventing effect was comparable to that of ranitidine treated rats. Level of glycoproteins was also found to be preserved in rats treated with the extract. The normal rats treated with the HAEAP did not show any abnormal alterations in the parameters studied. Histopathological observations also showed the ulcer preventing effect of the HAEAP. It is suggested that the ulcer preventing effect may be due to its mucin preserving and antioxidant nature.     

In vitro alpha-glucosidase and alpha-amylase enzyme inhibitory effects of Andrographis paniculata extract and andrographolide

There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study was to provide in vitro evidence for potential inhibition of alpha-glucosidase and alpha-amylase enzymes, followed by a confirmatory in vivo study on rats to generate a stronger biochemical rationale for further studies on the ethanolic extract of Andrographis paniculata and andrographolide. The extract showed appreciable alpha-glucosidase inhibitory effect in a concentration-dependent manner (IC(50)=17.2+/-0.15 mg/ml) and a weak alpha-amylase inhibitory activity (IC(50)=50.9+/-0.17 mg/ml). Andrographolide demonstrated a similar (IC(50)=11.0+/-0.28 mg/ml) alpha-glucosidase and alpha-amylase inhibitory activity (IC(50)=11.3+/-0.29 mg/ml). The positive in vitro enzyme inhibition tests paved way for confirmatory in vivo studies. The in vivo studies demonstrated that A. paniculata extract significantly (P<0.05) reduced peak blood glucose and area under curve in diabetic rats when challenged with oral administration of starch and sucrose. Further, andrographolide also caused a significant (P<0.05) reduction in peak blood glucose and area under the curve in diabetic rats. Hence alpha-glucosidase inhibition may possibly be one of the mechanisms for the A. paniculata extract to exert antidiabetic activity and indicates that AP extract can be considered as a potential candidate for the management of type 2 diabetes mellitus.     

Herb–drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats

Herb–drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of Andrographis paniculata extract (APE) and its major component, andrographolide (AG), on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. After APE or AG pretreatment for 3 days, on the fourth day rats were administered theophylline via femoral vein cannula. The blood theophylline levels were monitored by microdialysis sampling combined with HPLC-UV. The results indicated that the clearance of theophylline was significantly increased and the area under concentration–time curve (AUC) was reduced in both AG and APE pretreated groups at low-dose theophylline administration (1 mg/kg). The elimination half-life (t_1/2β) and mean residence time (MRT) of theophylline were shortened by 14% and 17%, respectively, in the AG pretreated group when high-dose theophylline (5 mg/kg) was given. However, theophylline accumulated in rat of the group with APE pretreatment. This phenomenon suggests that some other herbal components contained in APE may interact with theophylline and retard its elimination when theophylline was administered at a high dose. Our results suggest that patients who want to use CYP1A2-metabolized drugs such as caffeine and theophylline should be advised of the potential herb–drug interaction, to reduce therapeutic failure or increased toxicity of conventional drug therapy.     

Antioxidant and gastroprotective activities of Andrographis paniculata (Hempedu Bumi) in Sprague Dawley rats

Antioxidant and gastroprotective activities of aqueous and ethanolic extract of Andrographis paniculata leaves in rats have been reported. Sprague Dawley rats, 6 per group were used and rats in groups 1 to 6 were pretreated with (0.25% w/v) carboxymethyl cellulose (negative control, 5 ml/kg), 20 mg/kg omeprazole (positive control), (250 mg/kg and 500 mg/kg) of aqueous leaf extracts (APLAE) and (250 and 500 mg/kg) of ethanol leaf extracts (APLEE) respectively. Animals were orally administered with 95% ethanol (5 ml/kg) 60 min after their pretreatments. Rats were sacrificed 1 h after treatment and gastric contents were collected to measure pH and mucous weight. Stomach was analyzed for gross and histological changes. Ulcer control group showed extensive lesions of gastric mucosal layer, whereas rats pretreated with omeprazole, 250 and 500 mg/kg of APLAE showed significant and dose dependent reduction in gastric lesions with increased pH and mucus content of stomach. Rats pretreated with 250 or 500 mg/kg of APLEE showed significantly better inhibition of gastric mucosal lesions. Further, the in vitro antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that ethanol extracts have superior free radical scavenging activity with IC50 value = 10.9 than aqueous extracts with IC50 value = 24.65. Results of this study showed that pretreatment with ethonolic extract of A. paniculata ethanolic provided significant protection against gastric ulcer by regulating of pH, mucous production and antioxidant property.     

Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study.

The objective of our study was to measure the effectiveness of Andrographis paniculata SHA-10 extract in reducing the prevalence and intensity of symptoms and signs of common cold as compared with a placebo. A group of 158 adult patients of both sexes completed the randomized double blind study in Valdivia, Chile. The patients were divided in two equal size groups, one of which received Andrographis paniculata dried extract (1200 mg/day) and the other a placebo during a period of 5 days. Evaluations for efficacy were performed by the patient at day 0, 2, and 4 of the treatment; each completed a self-evaluation (VAS) sheet with the following parameters: headache, tiredness, earache, sleeplessness, sore throat, nasal secretion, phlegm, frequency and intensity of cough. In order to quantify the magnitude of the reduction in the prevalence and intensity of the signs and symptoms of common cold, the risk (Odds Ratio = OR) was calculated using a logistic regression model. At day 2 of treatment a significant decrease in the intensity of the symptoms of tiredness (OR = 1.28; 95% CI 1.07-1.53), sleeplessness (OR = 1.71; 95% CI 1.38-2.11), sore throat (OR = 2.3; 95% CI 1.69-3.14) and nasal secretion (OR = 2.51; 95% CI 1.82-3.46) was observed in the Andrographis SHA-10 group as compared with the placebo group. At day 4, a significant decrease in the intensity of all symptoms was observed for the Andrographis paniculata group. The higher OR values were for the following parameters: sore throat (OR = 3.59; 95% CI 2.04-5.35), nasal secretion (OR = 3.27; 95% CI 2.31-4.62) and earache (OR = 3.11; 95% CI 2.01-4.80) for Andrographis paniculata treatment over placebo, respectively. It is concluded that Andrographis paniculata had a high degree of effectiveness in reducing the prevalence and intensity of the symptoms in uncomplicated common cold beginning at day two of treatment. No adverse effects were observed or reported.     

Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation.

Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and antiatherosclerotic drug, was investigated for its suggested influence on the biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in isolated human polymorph-nuclear leukocytes (PMNL) no influence on the biosynthesis was found, it could be shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner (IC50-5 microM). These results indicate that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata.     

利用大孔树脂同时制备穿心莲内酯和脱水穿心莲内酯

采用大孔吸附树脂色谱法,以不同体积分数乙醇水溶液进行洗脱,分离富集穿心莲内酯和脱水穿心莲内酯,并配以HPLC进行同步监控.结果表明,穿心莲中这2种主要有效成分分别得到了富集.40%乙醇水溶液洗去目标物以外的杂质后,45%乙醇洗脱液中富含穿心莲内酯,含量为46.99%,55%乙醇洗脱液中富含脱水穿心莲内酯,含量为79.74%.     

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects.

The safety of different doses of Kan Jang--a fixed combination of Andrographis paniculata special extract (SHA-10) and Acanthopanax senticosus--compared to two extensively used medicinal plants, Valeriana officinalis and Panax ginseng in the form of standardized extracts, has been examined. A phase I clinical study was designed to evaluate the effect on semen quality of healthy males in terms of spermatogenesis and quality of semen. The results of the study revealed no significant negative effect of Kan Jang on male semen quality and fertility, but rather a positive trend with respect to the number of spermatozoids in the whole ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and fertility indexes, together with a decrease in the percentage of inactive (diskinetic) forms of spermatozoids. In the group receiving ginseng, no significant negative effects on the fertility parameters were revealed and there was a clear decrease in the percentage of diskinetic forms of spermatozoids. Subjects receiving valerian showed a temporary increase in the percentage of normokinetic spermatozoids and a decrease in diskinetic forms, but these changes had no effect on fertility indices. The results indicate that Kan Jang, ginseng and valerian are safe with respect to effects on human male sterility when administered at dose levels corresponding to approximately 3 times the human daily dose.     

In vitro antioxidant and anti-diabetic analysis of Andrographis echioides and Andrographis paniculata ethanol extract

It is of interest to analyse and compare the antioxidant and anti-diabetic activity of ethanolic extracts of Andrographis echioides and Andrographis paniculata. Andrographis echioides and Andrographis paniculata were collected from a local farm. In vitro antioxidant activity was assessed by the potential of Piperine, Lupeol, beta sitosterol; DPPH free radical scavenging assay was performed by Liyana Pathirana and Shahidi method. In vitro anti-diabetic activity was assessed by alpha amylase inhibitory activity and alpha glucosidase inhibitory activity. The data were analysed by one-way-ANOVA to check the statistical significance among the groups and considered at the levels of p<0.05. Both the ethanolic extracts of Andrographis echioides and Andrographis paniculata showed significant antioxidant and anti-diabetic potential in a dose-dependent manner (100-500µg) and can be used as potential antidiabetic agents. Similar to antioxidant potential, Andrographis paniculata exhibited an increased anti-diabetic potential compared to Andrographis echioides. Data shows that the ethanolic extracts of Andrographis echioides and Andrographis paniculata possessed antioxidant and anti-diabetic activity and hence our present findings conclude that both plants can be considered for the development of natural drugs for the management of diabetes.     

Andrographolide Induces Apoptosis in Gastric Cancer Cells through Reactivation of p53 and Inhibition of Mdm-2

Doklady Biochemistry and Biophysics - Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata. The plant extract and andrographolide has long been used in traditional...     

Chemical fingerprinting of Andrographis paniculata using HPLC, HPTLC and densitometry

An attempt has been made to develop a method by which to determine the chemical fingerprint of Andrographis paniculata (Acanthaceae). High-performance thin layer chromatography (HPTLC) was used to analyse hexane, chloroform, methanol and water extracts of leaves of A. paniculata. A computerised densitometer was applied to the two-dimensional spectrographic image analysis of the HPTLC plates. An HPLC equipped with a photodiode array detector was used for the analyses of these different extracts. The analyses showed that andrographolide and neoandrographolide are absent in the hexane extract but are present in greater amounts in the methanol extract as compared with the other extracts. These chromatograms may serve as a chemical fingerprint of the drug A. paniculata for quality control purposes and in the preparation of formulations based on the drug.     

Progesterone enhances ethanol-induced modulation of mesocortical dopamine neurons: antagonism by finasteride

The effect of endogenous 3α‐hydroxy‐5α‐pregnan‐20‐one (3α,5α‐TH PROG) on the modulation of mesocortical dopamine extracellular concentration by ethanol was investigated by microdialysis in rats. Intraperitoneal injection of progesterone (5 mg/kg, once a day for 5 days) increased the cortical content of 3α,5α‐TH PROG and potentiated the biphasic effect of acute intraperitoneal administration of ethanol on dopamine content. A dose of ethanol (0.25 g/kg) that was ineffective in naïve rats induced a 55% increase in dopamine extracellular concentration in rats pretreated with progesterone. This increase was similar to that induced by a higher dose (0.5 g/kg) of ethanol in naïve rats. Administration of ethanol at 0.5 g/kg to progesterone‐pretreated rats inhibited dopamine content by an extent similar to that observed with an even higher dose (1 g/kg) in naïve rats. The administration of the 5α‐reductase inhibitor finasteride (25 mg/kg, subcutaneous), together with progesterone, prevented the effects of the latter, both on the cortical concentration of 3α,5α‐TH PROG and on the modulation by ethanol of dopamine content. These data suggest that 3α,5α‐TH PROG contributes to the action of ethanol on the mesocortical dopaminergic system. They also suggest that physiological fluctuations in the brain concentrations of neuroactive steroids associated with the oestrous cycle, menopause, pregnancy and stress may alter the response of mesocortical dopaminergic neurons to ethanol.     

Infusion of pregnant rats with calcitonin gene-related peptide (CGRP)(8-37), a CGRP receptor antagonist,increases blood pressure and fetal mortality and decreases fetal growth

Calcitonin gene-related peptide (CGRP) is the most potent endogenous vasodilatory peptide, and is involved in the regulation of blood flow to vital organs. We have previously shown that CGRP may be involved in vascular adaptations that occur during pregnancy, and that steroid hormones may be involved in these mechanisms. We hypothesized that endogenous CGRP is required for maintaining blood pressure and fetoplacental growth in pregnant rats, and that progesterone will enhance CGRP effects. The vasodilatory effects of CGRP are known to be inhibited by a competitive CGRP receptor antagonist, the C-terminal fragment CGRP(8-37). In the present study, we investigated whether continuous s.c. infusion of CGRP(8-37) to pregnant rats will reduce fetoplacental growth and increase systolic blood pressure. We also assessed whether progesterone will alter the effects of CGRP(8-37) on blood pressure during postpartum. Groups of five pregnant rats were s.c. infused with varying doses of CGRP(8-37) from Day 17 of pregnancy. Daily systolic blood pressures, pup weight, mortality at term delivery, and fetoplacental weights on Day 20 of gestation were measured. CGRP(8-37) at a dose of 0.083 mg day(-1) kg(-1) body weight (BW) showed no effects; however, doses of 0.33 and 1.33 mg day(-1) kg(-1) BW increased (P < 0.05) blood pressure during pregnancy, and these elevated blood pressures persisted during postpartum with the highest dose used. Progesterone (2 mg per injection, twice a day; s.c.) treatment significantly elevated blood pressure in rats infused with CGRP(8-37) during postpartum, suggesting that progesterone regulates CGRP-induced vascular effects. CGRP(8-37) infusion caused significant reductions in pup weight with an increase in mortality rate, and these effects were dose-dependent. Placental and fetal weights were also decreased prior to term on Day 20 of gestation, 72 h after CGRP(8-37) infusion, indicating effects on uteroplacental tissues. Therefore, we suggest that endogenous CGRP plays an important role in maintaining normal fetoplacental development, fetal survival, and vascular adaptations during pregnancy.     

Free radical induced damages to rat liver subcellular organelles: inhibition by Andrographis paniculata extract

Aqueous extract of Andrographis paniculata was examined for antioxidant activity using rat liver subcellular organelles as model systems. The study deals with two important biological oxidative agents, ascorbate-Fe(+2) and AAPH generating hydroxyl and peroxyl radical, respectively. Oxidative damage was examined against the inhibition of membrane peroxidation, protein oxidation and restoration in decreased SOD and catalase activity. The antimutagenic activity of Ap was examined following inhibition in AAPH induced strand breaks in plasmid pBR322 DNA. Extract was a potent scavenger of DPPH, ABTS radicals, exemplified by ESR signals, O2-*, *OH and H2O2, displayed excellent reducing power, FRAP potentials to reduce Fe (III) --> Fe (II) and had considerable amount of phenolics/ flavonoids contents, an effective antioxidant index. The observed antioxidant effect might be primarily due to its high scavenging ability for ROS. Effect was confirmed ex vivo following inhibition in peroxidation, restoration in SOD enzyme, SOD band intensity and protein degradation in Ap fed liver homogenate. Based on these results, it was concluded that the aqueous extract of Andrographis paniculata might emerge as a potent antiradical agent against various pathophysiological oxidants.     

Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats

The effects of oral administration of aqueous extract of Bulbine natalensis Baker stem at daily doses of 25, 50, and 100 mg/kg body weight on the reproductive function of Wistar rats were evaluated. The indices of mating and fertility success as well as quantal frequency increased after 7 days of treatment in all the dose groups except the 100 mg/kg body weight group. The number of litters was not statistically different (P > 0.05) from the control. Whereas the absolute weights of the epididymis, seminal vesicle, and prostate were not affected, that of the testes was significantly increased. The epididymal sperm count, motility, morphology, and viscosity were not different from the control after 7 days of treatment. The male rat serum testosterone, progesterone, luteinizing hormone, and follicle-stimulating hormone significantly increased in the 25 and 50 mg/kg body weight groups, whereas the estradiol concentration decreased significantly at all the doses. The extract dose of 100 mg/kg body weight decreased the serum testosterone and progesterone levels in male rats. The prolactin concentration was not affected by all the doses. All the indices of reproduction, maternal, embryo/fetotoxic, teratogenic, and reproductive hormones in the female rats were not statistically different from that of their control except the resorption index, which increased at the dose of 100 mg/kg body weight of the extract. Histologic examination of the cross section of rat testes that received the extract at all the doses investigated revealed well-preserved seminiferous tubules with normal amount of stroma, normal population of spermatogenic and supporting cells, as well as normal spermatocytes within the lumen. The results revealed that the aqueous extract of Bulbine natalensis stem at doses of 25 and 50 mg/kg body weight enhanced the success rate of mating and fertility due to increased libido as well as the levels of reproductive hormones in male rats. The absence of alterations in the reproductive parameters of female rats at doses of 25 and 50 mg/kg body weight of Bulbine natalensis stem extract suggest that the extract is “safe” for use at these doses by females during the organogenic period of pregnancy, whereas the extract dose of 100 mg/kg body weight portends a negative effect on some reproductive functions of male and female rats.     

Synergetic effect of Andrographis paniculata polysaccharide on diabetic nephropathy with andrographolide

A water-soluble polysaccharide (APP), with a molecular weight of 4.6×10(4)Da, was isolated from Andrographis paniculata and gas chromatography (GC) analysis showed APP was composed of galactose, mannose, fucose, arabinose and rhamnose with molar ratios of 15.4:2.5:4.3:1.5:1.6. The synergetic effect of APP in combination with andrographolide on renal complication in streptozotocin (STZ) induced diabetic mice was investigated. Wistar rats were made diabetic by injection of STZ, and APP and/or andrographolide was administered to diabetic mice for continuous two weeks. APP plus andrographolide not only increased the body weight and creatinine clearance rate (Ccr), but also decreased the levels of serum creatinine, serum urea nitrogen, urinary albumin excretion (UAE), serum urea and blood glucose in diabetic rats, as well as the relative kidney weight. In summary, APP plus andrographolide can improve the metabolic abnormalities of diabetic mice and prevent or delay the progression of diabetic renal complications, which may be useful as a therapeutic agent for inhibiting the progression of diabetic nephropathy.     

The effects of progesterone supplementation on the metabolic clearance rate of progesterone in the pregnant rat

In the pregnant rat, short-term stability of progesterone blood concentrations may involve an active homeostatic mechanism. In the present study, we examined the possibility that the metabolic clearance rate (MCR) of progesterone can respond to a change in progesterone production and thus reduce variation in blood concentrations. Progesterone was administered both acutely and chronically to conscious rats, and the effective production rate, MCR, and blood concentration were monitored on Day 16 of pregnancy. Acute, low-dose progesterone supplementation, which effectively raised production rate by 29%, had no effect on the MCR of progesterone. Acute, high-dose supplementation, which raised total progesterone production by 68%, caused a 35% fall in the MCR of progesterone. Chronically supplemented rats received s.c. injections of progesterone (20 mg) once daily over Days 13-16 of pregnancy. The resultant production rate measured on Day 16 was 114% higher than that in controls, but there was no difference in MCR. Collectively, these experiments demonstrate that no short-term homeostatic mechanism involving the MCR operates to control blood progesterone concentrations in Day 16 pregnant rats. Thus, progesterone homeostasis appears limited to long-term developmental changes rather than short-term physiological control.