Abstract
Andrographis paniculata is well known medicinal plant of Ayurveda. It has been used as bitter tonic and febrifuge. Recent research has thrown light on medicinal value of the plant. A diterpene , Andrographolide is the active constituent and standardisation of Andrographis paniculata is based on Andrographolide content. The standardised extract contains 10% of Andrographoilde . The most significant pharmacological activities are anti-allergic and anti HIV effect.

Keywords
Andrographis paniculata/ Andrographolide /Medicinal herbs

Introduction
Andrographis paniculata is traditionally known as kalmegh . The plant belongs to family Acanthaceae and is widely used in Ayurvedic and Homeopathic systems of medicine. The plant grows in waste grounds and prefers moist habitat. The herb is bitter in taste and has weak odor. The whole plant is used in medicine. Due to the increasing demand the plant is cultivated also [1].In 1940, the medicine was part of the various prescriptions used for fever. The plant is official in Indian pharmacopoeia.

Common Names
Sanskrit: Bhunimba , Mahatikta
English: King of Bitters
Gujarati: Kiryato
Hindi: Kirat , Mahatita
Bengali: Kalmegh

Botany
The herb of Andrographis paniculata is an erect, annual and sometimes it assumes height of shrub also. The flowers of the plant are insignificant and of dirty pink color [2].In Ayurveda the drug has been described as antipyretic and hepatoprotective. Cold infusion of the drug is mentioned in Sushruta Samhita for fever and liver disorders.

Chemistry
Chemically the drug contains flavones and lactones. Among lactones Andrographolide is the main constituent and it also active principle of the plant. Andrographolide has been isolated in pure form and it has shown various pharmacological activities [3]. The herb also contains minerals and is a rich source of sodium chloride. Andrographis paniculata has been standardized to contain 10% of Andrographolide.The content of the active constituent of the herb is determined either by gravimetric method or by high performance liquid chromatography [HPLC].

Pharmacology
1. Hepatoprotective activity
Andrographis paniculata (AP) treatment prevents BHC induced increase in the activities of enzymes y- Glutamyl transpeptidase , glutathione-S- transferase and lipid peroxidation . The activities of antioxidant enzymes like superoxide dismutase , catalase , glutathione peroxidase and the levels of glutathione were decreased following BHC effect. Administration of AP showed protective effects in the activity of superoxide dismutase , catalase , glutathione peroxidase , glutathione reductase as well the level of glutathione. The activity of lipid peroxidase was also decreased. The result indicates antioxidant and hepatoprotective action of A. paniculata [4].

Alcoholic extract of the leaves of Andrographis paniculata was obtained by cold maceration. A dose of 300 mg/kg (1/6 of LD50) of the extract was selected to study hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters [5].

Andrographolide from the herb Andrographis paniculata (whole plant) per se produces a significant dose (1.5-12 mg/kg) dependent choleretic effect (4.8-73%) as evidenced by increase in bile flow, bile salt, and bile acids in conscious rats and anaesthetized guinea pigs. The paracetamol induced decrease in volume and content of bile was prevented significantly by andrographolide pretreatment. It was found to be more potent than silymarin , a clinically used hepatoprotective agent [6].

2. Hypoglycemic activity
So far known Andrographis paniculata) is a hepatoprotective, antiplatelet and antithrombotic drug. In this experiment its hypoglycaemic effect has been tried in various ways. Water extract of AP 10 mg/kg body weight can prevent induction of hyperglycaemia significantly (P < 0.001) induced by oral administration of glucose 2 mg/kg body weight. But any how failed to do so in adrenaline induced hyperglycaemia . It also failed to demonstrate any "fasting blood sugar lowering effect" upon chronic administration (6 weeks) of AP. So probably AP prevents glucose absorption from gut. Whole experiment was done on rabbits [7].

4 . Cardiovascular activity
To observe the effects of Andrographis Paniculata component on nitric oxide, endothelin , cyclic guanosine monophosphate , lipid peroxide and superoxide dismutase in experimental atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and andrographis paniculata treated group. Blood samples were collected before 4 weeks and 8 weeks after relevent treatment. Before 4 and after 8 weeks andrographis paniculata administration, compared with model group, the nitric oxide, cyclic guanosine monophosphate and activity of superoxide dimutase increased, while lipid peroxide and endothelin decreased .it was concluded that andrographis paniculata possesses the effects of antioxidation , preserving endothelial function, and maintaining the balance of nitric oxide/ endothelin [9].


5. Psycho- pharmacological activities
Psychopharmacological studies were conducted on an extract of Andrographis paniculata herbs. The extract exhibited a significant alteration in behavior pattern and a reduction in spontaneous motility. The extract also produced a prolongation of the pentobarbitone -induced sleeping time and lowered the body temperature in different experimental animal models [10].

6. Anti -HIV activity
A phase I dose-escalating clinical trial of andrographolide from Andrographis paniculata was conducted in 13 HIV positive patients and five HIV uninfected, healthy volunteers. The objectives were primarily to assess safety and tolerability and secondarily to assess effects on plasma virion HIV-1 RNA levels and CD4 (+) lymphocyte levels. No subjects used antiretroviral medications during the trial. Those with liver or renal abnormalities were excluded. The planned regimen was 5-mg/kg bodyweight for 3 weeks, escalating to 10-mg/kg bodyweight for 3 weeks and to 20-mg/kg bodyweight for a final 3 weeks. The trial was interrupted at 6 weeks due to adverse events including an anaphylactic reaction in one patient. All adverse events had resolved by the end of observation. A significant rise in the mean CD4 (+) lymphocyte level of HIV subjects occurred after administration of 10 mg/kg andrographolide (from a baseline of 405 cells/mm (3) to 501 cells/mm (3); p = 0.002). There were no statistically significant changes in mean plasma HIV-1 RNA levels throughout the trial. Andrographolide may inhibit HIV-induced cell cycle dysregulation , leading to a rise in CD4 (+) lymphocyte levels in HIV-1 infected individuals [11]

7. Anti -allergic activity
One study, conducted by C?ceres , Hancke , et al., measured the effectiveness of Andrographis SHA-10 extract, compared against a placebo, in lessening the symptoms associated with the common cold. With a patient group of 158 male and female adults, the effects of Andrographis were measured on days 0, 2, and 4 of the treatment. On day 2, the patient group taking Andrographis displayed reductions in several of the associated symptoms, and on day 4, the same group was shown to have significant reductions in all of the symptoms as compared to the placebo group. In the summary conclusion, C?ceres , Hancke , et al. write, "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 reported [12].

In another study conducted by C?ceres , Hancke et al., one group of students in a rural school was given a placebo and another was given Kan Jang, a formulation of Andrographis paniculata from the Swedish Herbal Institute, and then observed to see how many colds occurred over a three month period. A dose of 200 mg a day was given to the study group, and after 1 month no significant difference was recorded. But after three months, significant variances occurred. The Kan Jang group was 2.1 times less likely to catch a cold than the placebo group. They had a rate of incidence of 30 percent, compared to 62 percent in the placebo group [13]

Toxicity
The possible testicular toxicity of Andrographis paniculata, standardized dried extract was evaluated in male Sprague Dawley rats for 60 days. No testicular toxicity was found with the treatment of 20, 200 and 1000 mg/kg during 60 days as evaluated by reproductive organ weight, testicular histology, ultrastructural analysis of Leydig cells and testosterone levels after 60 days of treatment. It is concluded that Andrographis paniculata dried extract did not produce subchronic testicular toxicity effect in male rats [14].

References
1. Zhong Yao Cultivation of Andrographis paniculata. Tong Bao 1987 Jun;12(6): 15-18

2. Chen JH, Jiang RL. Morphological and histological studies on Andrographis paniculata ( Burm . F.) Nees. and comparison with four other Acanthaceae herbs. Yao Xue Xue Bao 1980 Dec;15 (12): 750-760.

3. 3.Hu CQ, Zhou BN. Isolation and structure of two new diterpenoid glucosides from Andrographis paniculata Nees. Yao Xue Xue Bao 1982 Jun;17(6): 435-440

4. Trivedi NP, Rawal UM. Hepatoprotective and antioxidant property of Andrographis paniculata ( Nees ) in BHC induced liver damage in mice. Zoology Department, Gujarat University, Ahmedabad 380009, India. Indian J Exp Biol 2001 Jan;39 (1): 41-46.

5. Shukla B, Visen PK , Patnaik GK, Dhawan BN. Choleretic effect of andrographolide in rats and guinea pigs. ICMR Centre for Advanced Pharmacological Research on Traditional Remedies, Central Drug Research Institute, Lucknow, India. Planta Med 1992 Apr; 58 (2): 146-149.

6. Rana AC, Avadhoot Y. Hepatoprotective effects of Andrographis paniculata against carbon tetrachloride-induced liver damage. College of Pharmacy, Shri Govindram Seksaria Institute of Technology and Science, Indore, India. Arch Pharm Res 1991 Mar;14 (1): 93-95.

7. Borhanuddin M, Shamsuzzoha M, Hussain AH. Hypoglycaemic effects of Andrographis paniculata Nees on non-diabetic rabbits. Dhaka Medical College, Bangladesh. Bangladesh Med Res Counc Bull 1994 Apr ;20 (1): 24-26.

8. Zoha MS, Hussain AH, Choudhury S. Antifertility effect of andrographis paniculata in mice. Bangladesh Med Res Counc Bull 1989 Jun; 15 (1): 34-37.

9. Wang HW, Zhao HY, Xiang SQ. Effects of Andrographis paniculata component on nitric oxide, endothelin and lipid peroxidation in experimental atherosclerotic rabbits. Zhongguo Zhong Xi Yi Jie He Za Zhi 1997 Sep ;17 (9): 547-549.

10. Mandal SC, Dhara AK , Maiti BC . Studies on psychopharmacological activity of Andrographis paniculata extract. Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032, India. Phytother Res 2001 May; 15 (3): 253-256.

11. Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA, Standish LJ. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Bastyr University Research Institute, Bastyr University, Washington 98028, USA. Phytother Res 2000 Aug; 14 (5): 333-338.

12. C?ceres D.D., J.L. Hancke , R.A. Burgos, F. Sandberg, G.K. Wikman . 1999. Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardizing Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 6(4): 217-223.

13. C?ceres D.D., J.L. Hancke , R.A. Burgos, G.K. Wikman . 1997. Prevention of common colds with Andrographis paniculata dried extract. A Pilot double blind trial. Phytomedicine. 4(2): 101-104.

14. Burgos RA, Caballero EE, Sanchez NS , Schroeder RA, Wikman GK, Hancke JL.
Instituto de Farmacologia, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia.J Ethnopharmacol 1997 Nov; 58(3): 219-224.