A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.

A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10 fixed combination, Kan Jang, in the treatment of acute upper respiratory tract infections, including sinusitis. Ninety-five individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. The medication was taken for 5 days. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the verum group versus the placebo. This result applied to the group as a whole and to the sinusitis subgroups. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduced in the verum group. It can be concluded that Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.     

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.     

Biosynthesis of andrographolide in Andrographis paniculata

Andrographolide, a diterpene lactone, is isolated from Andrographis paniculata which is well known for its medicinal properties. The biosynthetic route to andrographolide was studied using [1-¹³C]acetate, [2-¹³C]acetate and [1,6-¹³C₂]glucose. The peak enrichment of eight carbon atoms in the ¹³C NMR spectra of andrographolide suggested that deoxyxylulose pathway (DXP) is the major biosynthetic pathway to this diterpene.The contribution of the mevalonic acid pathway (MVA) is indicated by the observed ¹³C-labeling pattern, and because the labeling patterns indicate a simultaneous contribution of both methyl erythritol phosphate (MEP) and MVA pathways it can be deduced that cross-talk occurs between plastids and cytoplasm.     

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.     

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.     

Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection.

Two randomized double-blind, placebo-controlled parallel group clinical trials were performed to investigate the effect of a standardized extract (SHA-10) of Andrographis paniculata fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infections. 46 patients in the pilot study and 179 patients in the phase III study completed the study according to the protocol. Medication was taken three times daily for a minimum of 3 days and a maximum of 8 days for the pilot study, and for exactly three days in the phase III study. The primary outcome measures in the patients self-evaluation were: related to pain in the muscle, cough, throat symptoms, headache, nasal symptoms and eye symptoms and temperature. The physician's fixed score diagnosis was based mainly on sign/symptoms: ears, nose, oral cavity, lymph glands-tonsils and eyes. The total symptom score showed a tendency toward improvement in the pilot study (p = 0,08), while both the total symptom score and total diagnosis score showed highly significant improvement (p < or = 0.0006 resp. 0.003) in the verum group as compared with the placebo. In both studies throat symptoms/signs, were found to show the most significant improvement.     

The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of warfarin in rats.

Significant pharmacokinetic/pharmacodynamic interactions between various herbal products and warfarin have recently been reported. The aim of this study was to determine whether concomitant treatment of rats with Kan Jang (a standardized fixed combination of extracts from Andrographis paniculata and Eleutherococcus senticosus) and warfarin would lead to an alteration in the pharmacological effects of warfarin. Each day for 5 days a group of animals was treated orally with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active principle andrographolide (a daily dose some 17-fold higher than that recommended for humans): the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml) was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration and blood samples taken. The concentration of warfarin in blood plasma was measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm. Prothrombin time in blood plasma was measured using thromboplastin reagent. The concomitant application of Kan Jang and warfarin did not produce significant effects on the pharmacokinetics of warfarin, and practically no effect on its pharmacodynamics.     

Determination of andrographolide,deoxyandrographolide and neoandrographolide in the Chinese herb Andrographis paniculata by micellar electrokinetic capillary chromatography

In this paper a micellar electrokinetic capillary chromatographic (MEKC) method has been developed for determining the active components (andrographolide, deoxyandrographolide and neoandrographolide) in water:ethanol extracts of the Chinese crude herb Andrographis paniculata and its preparations (Chuanxinlian and Xiaoyan Lidan tablets). The optimum separation conditions were 15 mM sodium dodecyl sulphate in 30 mM borate buffer (pH 9.5) with UV detection wavelength at 214 nm and a constant voltage of 16 kV. An HPLC method was employed in order to validate the MEKC method with respect to separation efficiency, sensitivity, linearity and repeatability. The two methods are shown to be complementary because of their different selectivity and thus are very suitable for cross-validation studies. The MEKC method is demonstrated to be more appropriate for the analysis of the active compounds in A. paniculata in that it is easier and less expensive to use and does not suffer from contamination of the chromatographic column.     

Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats.

The effect of the powdered extract of Andrographis paniculata leaves (APE), an active principle of Kan Jang tablets [standardized for content of andrographolide (4.6%) and 14-deoxo-andrographolide (2.3%) content (total andrographolids--6.9%)] on blood progesterone content in rats was studied. Peroral administration of APE during the first 19 days of pregnancy in doses of 200, 600, and 2000 mg/kg (i.e. doses 30, 90, and 300 fold higher than its daily therapeutic dose in humans) does not exhibit any effect on the elevated level of progesterone in the blood plasma of rats. Let us assume then that in therapeutic dose, Andrographis paniculata extract cannot induce progesterone-mediated termination of pregnancy.     

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.     

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.     

Molecular docking analysis of phytocompounds from Andrographis paniculata binding with proteins in the notch-signaling pathway

It is of interest to document the molecular docking analysis of phytocompounds from Andrographis paniculata binding with protein NOTCH1 in the Notch-signaling pathway in the context of cancer. Hence, we document the binding features of neoandrographolide, 14-deoxyandrographolide, androgapholide and andrograpanin with proteins in the notch-signaling pathway for further consideration.     

Three Salts of Labdanic Acids from Andrographis paniculata (Acanthaceae) (in English)

Three salts of labdanic acids, named as magnesium andrographate, disodium andrographate and dipotassium andrographate 19-O-β-D-glucoside were isolated from the hydrophilic extract of Andrographis paniculata Nees. (Acanthaceae), together with guanosine, uridine, 6-epiharpagide, procumbide, violanthin and apigenin 7-O-β-D-glucoside. Their structures were determined by spectroscopic analysis and chemical transformation.     

The rate and extent of calcium bioavailability from two oral dosage forms in rats

The purpose of the present work was to compare oral bioavailability of calcium from two calcium preparations, Calcium Sandoz forte 500 mg and Calcium Spofa effervescens. The pharmacokinetic study was carried out on rats, and plasma levels of 45Ca after administration of labelled calcium solutions were determined. Appropriate equations describing the two-compartment open model and the one-compartment model with first order absorption were fitted to the observed i.v. and oral data, respectively, using weighted nonlinear least-squares regression analysis. The extent and the time profile of the rate of 45Ca systemic bioavailability were assessed. Both parameters suggested identical bioavailability of calcium from the two dosage forms compared.     

Intra-specific hybridization: generator of genetic diversification and heterosis in Andrographis paniculata Nees. A bridge from extinction to survival

Andrographis paniculata (AP) has been stated as a low-diverse, endangered and red-listed plant species. Self-pollinated mating system, being an introduced species and experiencing a bottleneck as well as over exploitation cause such a consequence. Inter and intra-specific hybridizations have been suggested as essential techniques for generating genetic diversity. To test the effect of intra-specific hybridization on diversification and heterosis of AP, seven accessions were outcrossed manually in all 21 possible combinations. Three types of markers including morphological, phytochemical and RAPD markers were employed to evaluate the mentioned hypothesis. The results revealed that hybridization acted as a powerful engine for diversification of AP as it caused heterotic expression of the studied traits, simultaneously. Initially, it seems that additive and non-additive gene effects both can be considered as the genetic basis of heterosis in AP for the investigated traits. Agronomic and morphological traits were differentiated from each other, while positive heterosis was recorded mainly for agronomic traits but not for the morphological traits. Intra-specific hybridization increased the genetic diversity in AP population. Nevertheless, a part of this variation could also be attributed to the negative heterosis. The current exploration demonstrated the first ever conducted manual intra-specific hybridization among AP accessions in a mass scale. However, the 17 RAPD primers produced a monomorph pattern, but perhaps increasing the number of markers can feature a new genetic profile in this plant.     

Determination and variation of three active diterpenoids in Andrographis paniculata (Burm.f.) Nees

Simple and rapid methods have been developed for the extraction and simultaneous determination of the three active diterpenoids, andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4), from various samples of Andrographis paniculata (Burm.f.) Nees. Methanol extracts from the dried leaves, stems and crude products were analysed by isocratic HPLC using a methanol and water mobile phase with monitoring at 220 nm. There was a large variation of the three active diterpenoids in different A. paniculata products obtained from Thai markets. The results indicated that the amounts of these active compounds consumed, based on the recommended daily doses, from materials obtained from the different suppliers will be different. In addition, the stability of these three active compounds was also examined in dry herbs stored at room temperature. The results showed that andrographolide was more stable than the others. In contrast, the content of 14-deoxy-11,12-didehydroandrographolide increased and the neoandrographolide content fluctuated during storage time. The combination of different levels of these compounds in the source materials and the changes during storage could have a significant effect on the efficacy of this traditional herbal medicine in clinical treatment.     

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     

Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats

Cyclosporin, an immunosuppressant with a narrow therapeutic window, is a substrate for both CYP3A4 and P-glycoprotein (Pgp). Quercetin is an inhibitor of CYP3A4 and a modulator of Pgp. This study aimed to measure the effect of quercetin on the absorption and disposition of cyclosporin in pigs and rats. Cyclosporin (Sandimmune, 10 mg/kg) was orally administered with and without a concomitant dose of quercetin (50 mg/kg) to pigs and rats. Cyclosporin concentrations in blood samples were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters were calculated by noncompartmental analysis using WINNONLIN. A paired Student's t-test was conducted for statistical comparison. A study using the everted intestinal sac was carried out to evaluate the effect of quercetin on the function of intestinal Pgp. The coadministration of quercetin significantly decreased cyclosporin AUC(0-3) (area under the concentration-time curve from time zero to 3 h) by 56% and AUC(0-t) (area under the concentration-time curve from time zero to the last point) by 43% in pigs and rats, respectively, indicating that the coadministration of quercetin significantly decreased cyclosporin oral bioavailability. However, the inverted sac study showed that quercetin significantly inhibited the function of intestinal Pgp. It is suggested that concurrent use of quercetin or quercetin-containing dietary supplement or herbs with cyclosporin or other medications whose absorption and metabolism are mediated by Pgp and/or CYP3A4 should require close monitoring.