INTRODUCTION:

Medicinal plants are in prevalence from the origin of the earth which has been efficiently used by ancient people as a treatment for various diseases. The plant extracts are identified and act as an important source of active ingredient and secondary metabolite products such as alkaloid, terpenoids, which is used in therapeutic diseases, for drug production and maintaining good health by both the traditional and orthodox medical practitioners.

The current aim of this review is to accumulate the morphological and pharmacological applications of Andrographis paniculata as a multipurpose drug showing efficient activity in curing various diseases. The phytochemical tests revealed the presence of glycosides, saponins, tannins and alkaloids, but not of anthraquinones. Thus the plant has an important compound named as Andrographolide, a diterpenoid lactone having a diversity of pharmacological effects. The over dosage of the plant leads to some side effects like nausea, vomiting and loss of appetite Therefore, researchers have to perform various formulation for A. paniculata and develop a new drug molecules. The plant is considered as a safe, highly important medicinal plant for mankind.^[1,2]

Andrographis paniculata (Burm. F.) Wall. Ex Nees (AP) also called Kalmegh or "King of Bitters” belongs to family Acanthaceae. It has been used for centuries in Asia to treat gastro-intestinal tract and upper respiratory infections, fever, herpes, sore throat, and a variety of other chronic and infectious diseases. Itis an annual and branched plant with lanceolate green leaves and attains heights of 60-70 cm. It grows abundantly in Asian countries like India, Sri Lanka, Pakistan, Java, Malaysia and Indonesia and is one of the commonly used medicinal plants in Ayurvedic and Unani systems of medicines. The plant is also known as the ‘king of bitters’ because it is extremely bitter in taste in every part of plant body.^[3,4]

Andrographis paniculata (Nees), is a valuable traditional medicinal plant and it has many important bioactive compounds. It cures and prevents a number of diseases in human beings. It is a boon of the nature of human healthy life. It cures cold, fever, colic pain, active against inflammatory, antidiabetic activity, antioxidant, antifertility, cardiovascular and anti-virus including inhibited HIV. In this present study, the bioactive compounds were analyzed using IR, NMR spectrum, and GC-MS. Many of these compounds found were effectively used for human benefits.^[7,8,22]

TAXONOMICAL CLASSIFICATION:-

1. Kingdom: Plantae, Plants

2. Sub Kingdom: Tracheobionta, Vascular plants;

3. Super Division : Spermatophyta, Seed plants;

4. Division: Angiosperma

5. Class: Dicotyledonae

6. Sub class: Gamopetalae

7. Series: Bicarpellatae

8. Order: Personales

9. Tribe: Justicieae

10. Family: Acanthaceae

11. Genus: Andrographis

12. Species: A. paniculata(Burm. f) Nees

BOTANICAL DESCRIPTION:

AP is an annual, branched, herbaceous plant erecting to a height of 30-110 cm in moist shady places with stem acutely quadrangular, much branched, easily broken fragile texture stem. Leaves are simple, opposite, lanceolate, glabrous, 2–12cm long, 1–3cm wide with margin acute and entire or slightly undulated and upper leaves often bractiform with short petiole. Inflorescence of the plant is characterized as patent, terminal and axillary in panicle, 10–30 mm long; bract small; pedicel short. The flowers possess botanical features of calyx 5-particle, small, linear; corolla tube narrow, about 6 mm long; limb longer than the tube, bilabiate; upper lip oblong, white with a yellowish top; lower lip broadly cuneate, 3-lobed, white with violet markings; stamens 2, inserted in the throat and far exserted; anther basally bearded. Superior ovary, 2-celled; style far exserted. Capsule of the plant is erect, linear-oblong, 1–2 cm long and 2–5 mm wide, compressed, longitudinally furrowed on broad

faces, acute at both ends, thinly glandular-hairy. Seeds are very small, subquadrate.^[41,42]

MORPHOLOGY OF ANDROGRAPHIS PANICULATA

A) Mature seeds B) Leaves C) Aerial parts with mature and immature capsule; D) Flower buds E) Entire flower F) Mature Fruit.

Table: Morphological Characters of Andrographis paniculata.^[26,27,28]

1.	Plant height	30–110 cm
2.	Stem	Dark green
	Length	30–100 cm
	Diameter	2–6 mm
	Shape	Quadrangular with longitudinal furrows and wings on the angles of the young parts, slightly enlarged at the nodes
3.	Leaves	Glabrous
	Length	2–12 cm
	Width	1–3 cm
	Arrangement	Lanceolate
	Shape	Pinnate, acute apex, entire margin
4.	Flowers	White with rose-purple spots on the petals
	Size	Small, in lax spreading axillary and terminal racemes or panicles
5.	Seed	Capsules linear-oblong, acute at both ends
	Size	1.9 cm × 0.3 cm
	Color	Yellowish brown
	Shape	Subquadrate, numerous
6.	Flowering and fruiting	December to April

Table: Pharmacological activity of Andrographis paniculata.

S.no

Pharmacological activity

References

Anti-inflammation–

i) LPS-induced NO production by suppressing iNOS.

ii) Complement 5a-induced macrophage recruitment via ERK1/2 and PI3K signal pathways.

iii) Binding of NF-κB oligonucleotide to nuclear proteins via _ERK1/2 or PI3/AKt signal pathway.

[18,31,29]

Anti-cancer–

i) Proliferation of HL-60 cells, the JAK-STAT3 pathway.

ii) Tumor suppressor p53 expression, MAPKs (p38 kinase, JNK, ERK1/2) signaling pathway.

iii) oncogene v-Src protein expression and v-Src-induced transformation.

iv) Tumor in melanoma subcutaneously implanted mice (orally 200, 400 mg/kg BW, 10d).

[11,19,20]

Immunomodulation–

i)Proliferation and IL-2 induction in hPBL.

ii) antibody and the delayed-type hypersensitivity response (orally 1 mg/kg, 7d).

iii) NF-κB expression in lung and airway epithelial cells infiltration of inflammatory cells in lung, airway hyperreactivity (i.p. 2 μg/g BW, 7d).

iv) LPS induced dopaminergic neurodegeneration in primary rat mesencephalic neuron-glial cultures.

v) IL-2 production, proliferation, antibody production, T cell activation in EAE (i.p. 4 mg/kg BW).

vi) Symptom and immunological markers in patients with RA (30% androographolide tablet, 14 weeks).

[38,39,40]

Anti-infection-

HIV induced cell cycle dysregulation, CD4+lymphocyte levels in HIV-1 infected individualsviricidal activity against HSV-1, EBV, via producing mature virus particle.

[37]

Anti-hepatotoxicity-

i) CYP1A1 and CYP1A2 mRNA in mouse hepatocytes, synergistic effect in with a CYP1A1 inducer.

ii) Expression of the pi class of glutathione S-transferase.

[35,36]

Anti-atherosclerosis-

i)HUVECs apoptosis via enhancement of PI3K-Akt activity.

ii) Thrombin-induced platelet aggregation via ERK1/2 pathway.

[31,32]

Anti-hyperglycemic effect-

i)Plasma glucose concentrations of STZ-diabetic rats(oral 1.5 mg/Kg).

ii) mRNA and protein levels of GLUT4 in soleus muscle.

[33,34]

Anti-Oxidation-

i)MDA formation .

ii) GSH, SOD activity.

[15]

Pharmacological Properties of Andrographolide:

TABLE: Bioactivities of compounds isolated from A. paniculata.

S.no	Plant	Chemical Constituents	Pharmacological action	Models	References
1.	ANDRO.PANI.	Andrographolides.	Anticancer, Bioactivities&Hepatoprotective. Andrographolide has also beenreported to suppress IL-2 production and T-cell proliferation in a mixed lymphocyte reaction and to inhibit dendritic cell maturation and antigen presentation.	In vivo models of the anticancer activity of andrographolide have been used against MCF-7 and HT-29 tumor xenografts and B16F0 melanoma . In a radiation therapy study, andrographolide was found to sensitize Rastransformed cells and significantly delay tumor growth. Their experimental evidence suggests that andrographolide attenuates endothelial cell motility and tumor-endothelial cell interaction.	(9,16).
2.	-	14-deoxyandrographolide	Activation of NOS and guanylatecyclasevaso relaxation in vitro and in vivo, enhanced proliferation and interleukin-2 induction in human peripheral blood lymphocytes.	In-vitro & in-vivo methods.	(16,31,25)
3.	-	Neoandrographolide	NO, PGE2, iNOS and COX-2 in activated macrophages CCl4, tBHP-induced hepatotoxicity (i.p100 mg/kg, 3d).	In vivo and in vitro for its anti-inflammatory activities and mechanism. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of neoandrographolideon suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α).	(5,6,15)
4.	-	14-deoxy-11,12-didehydroandrographolide	Muscle relexation, NO release from endothelial cells and anticancer.	In-vitro & in-vivo methods.	(16,17)
5.	-	14-deoxy-14,15-didehydroandrographolide	cytotoxic activity and cell cycle arrest of tumor cells NF-κB-dependent trans-activation.	In-vitro & in-vivo methods.	(9,29)
6.	-	Andrograpanin	protein kinase or p38 MAPKs pathways chemokine SDF-1α induced chemotaxis in Jurkat andTHP-1 cells.	-	(32,14)
7.	-	Isoandrographolide	cell-differentiation-inducing activity proliferation of HL-60 cells.	-	(13,10)
8.	-	14-acetylandrographolide	Growth of leukeamia, ovarian,renal cancer cells.	-	(12)
9.	-	19-Oacetylanhydroandrographolide	NF-κB-dependent trans-activation.	-	(17)
10	-	Andrographide	Liver cleansing and hepatitis.	-	(20)
11	-	Kalmeghin	Fever & cold	-	(21)
12	-	Andrographiside	Anti-oxidant, anti-lipoperoxidant, carcinogenic & detoxification.	-	(22,23)

REFERENCES:

1. Patra A, Mitra AK: Carbon-13 NMR spectra of some labdanediterpenoids. Org MagnReson1981, 17 (4):301-302.

2. Fujita T, Fujita R, Takeda Y, Takaishi Y, Yamada T, Kido M, Miura I: On the diterpenoids of Andrographis paniculata: X-ray crystallographic analysis of and rographolide and structure determination of new minor diterpenoids. Chem Pharm Bull (Tokyo) 1984, 32 (6):2117-2125.

3. Davi G, Falco A: Oxidant stress, inflammation and atherogenesis. Lupus 2005, 14:760-764.

4. O'Shea JJ, Murray PJ: Cytokine signaling modules in inflammatory responses. Immunity 2008, 28 (4):477-87.

5. Batkhuu J, Hattori K, Takano F, Fushiya S, Oshiman KI, Fujimiya Y: Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata. Biol Pharm Bull 2002, 25:1169-1174.

6. Liu J, Wang ZT, Ji LL, Ge BX: Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage. Mol Cell Biochem 2007, 298:49-57.

7. Liu J, Wang ZT, Ji LL: In vivo and in vitro anti-inflammatory activities of Neoandrographolide. Am J Chin Med 2007, 35:317-328.

8. Liu J, Wang ZT, Ge BX: Andrograpanin, isolated from Andrographis paniculata, exhibits anti-inflammatory property in lipopolysaccharide Induced macrophage cells through down regulating the p38 MAPKs signaling pathways. IntImmunopharmacol 2008, 8:951-958.

9. Geethangili M, Rao YK, Fang SH, Tzeng YM: Cytotoxic constituents from Andrographis paniculata in duce cell cycle arrest in Jurkat cells. Phytother Res 2008, 22:1336-1341.

10. Chen L, Zhu H, Wang R, Zhou K, Jing Y, Qiu F: ent-Labdanediterpenoid lactone stereoisomers from Andrographis paniculata. J Nat Prod 2008, 71:852-855.

11. Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R: Andrographolide, a potential cancer therapeutic agent isolated from Andrographispaniculata. J Exp Ther Oncol 2003, 3:147-158.

12. Jada SR, Suseno GS, Matthews C, Hamzah AS, Lajis NH, Saad MS, Stevens MFG, Stanslas J: Semisynthesis and in vitro anticancer activities of andrographolide analogues. Phytochemistry 2007, 68:904-912.

13. Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K: Cell differentiation inducing diterpenes from Andrographis paniculata Nees. Chem Pharm Bull (Tokyo) 1994, 42:1216-1225.

14. Ji LL, Wang Z, Dong F, Zhang WB, Wang ZT: Andrograpanin, a compound isolated from anti-inflammatory traditional Chinese medicine Andrographis paniculata, enhances chemokine SDF-1α-induced leukocytes chemotaxis. J Cell Biochem2005, 95:970-978.

15. Kapil A, Koul IB, Banerjee SK, Gupta BD: Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochem Pharmacol 1993, 46 (1):182-185.

16. Zhang CY, Tan BK: Effects of 14-deoxyandrographolide and 14-deoxy-11,12-didehydroandrographolide on nitric oxide production in cultured human endothelial cells. Phytother Res 1999, 13:157-159.

17. Yoopan N, Thisoda P, Rangkadilok N, Sahasitiwat S, Pholphana N, Ruchirawat S: Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts. Planta Med 2007, 73:503-511.

18. Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X: And rographolide attenuates inflammation by inhibition of NF-κB activation through covalent modification of reduced cysteine 62 of p50. J Immunol2004, 173:4207-4217.

19. Zhou J, Zhang S, Ong CN, Shen HM: Critical role of pro-apoptotic Bcl-2 family members in andrographolide induced apoptosis in human cancer cells. Biochem Pharmacol2006, 72:132-144.

20. Zhou J, Lu GD, Ong CS, Ong CN, Shen HM: Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53 mediated beath receptor 4 up-regulation. Mol Cancer Ther2008, 7 (7):2170-2180.

21. Yang L, Wu D, Luo K, Wu S, Wu P: Andrographolide enhances 5-fluorouracil induced apoptosis via caspase 8 dependent mitochondrial pathway involving p53 participation in hepatocellular carcinoma (SMMC-7721) cells. Cancer Lett2009, 276:180-188.

22. Liang FP, Lin CH, Kuo CD, Chao HP, Fu SL: Suppression of v-Src transformation by andrographolide via degradation of the v-Src protein and attenuation of the Erksignaling pathway. J Biol Chem2008, 283 (8):5023-5033.

23. Shi MD, Lin HH, Chiang TA, Tsai LY, Tsai SM, Lee YC, Chen JH: Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down regulation of MMP-7 expression. ChemBiol Interact 2009, 180:344-352.

24. Abu-Ghefreh AA, Canatan H, Ezeamuzie CI: In vitro and in vivo anti-inflammatory effects of andrographolide. Int Immunopharmacol 2009, 9:313-318.

25. Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Caceres DD: Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo controlled trial. Clin Rheumato l2009, 28:931-946.

26. Mishra SK, Sangwan NS, Sangwan RS. Andrographis paniculata (Kalmegh): A review, Pharmacognosy Reviews, 2007; 1:283-298.

27. Kabeeruddin M, Kitabul Advia, 2, Aligarh Barqi Press, Delhi, 1937, 148-150.

28. Shahid A, Andrographis paniculata: A review of pharmacological activities and clinical effects, Alternative Medicine Review, 2011; 16:66-77.

29. Chao WW, Kuo YH, Lin BF: Anti-inflammatory Activity of New Compounds from Andrographis paniculata by NF-κB Trans-Activation inhibition. J Agric Food Chem2010, 58:2505-2512.

30. Zhang CY, Tan BK: Vasorelaxation of rat thoracic aorta caused by 14- deoxyandrographolide. Clin Exp Pharmacol Physiol 1998, 25:424-429.

31. Chen JH, Hsiao G, Lee AR, Wu CC, Yen MH: Andrographolide suppresses endothelial cell apoptosis via activation of phosphatidyl inositol-3-kinase/Akt pathway. Biochem Pharmacol 2004, 67:1337-1345.

32. Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J: Inhibitory effect of Andrographis paniculata extract andits active diterpenoids on platelet aggregation. Eur J Pharmacol 2006, 553:39-45.

33. Yu BC, Hung CR, Chen WC, Cheng JT: Antihyperglycemic effect of andrographolide in streptozotocin induced diabetic rats. Planta Med 2003, 69:1075-1079.

34. Yu BC, Chang CK, Su CF, Cheng JT: Mediation of β-endorphin in and rographolide induced plasma glucose lowering action in type I diabetes like animals. Naunyn-Schmiedeberg's Arch Pharmacol 2008, 377:529-540.

35. Jaruchotikamol A, Jarukamiorn K, Sirisangtrakul W, Sakuma T, Kawasaki Y, Nemoto N: Strong synergistic induction of CYP1A1 expression by and rographolide plus typical CYP1A inducers in mouse hepatocytes. Toxicol Appl Pharmacol2007, 224:156-162.

36. Chatuphonprasert W, Jarukamjorn K, Kondo S, Nemoto N: Synergistic increases of metabolism and oxidation reduction genes on their expression after combined treatment with a CYP1A inducer and andrographolide. Chem Biol Interact 2009, 182:233-238.

37. Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Well K, Wenner CA, Standish LJ: A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res 2000, 14:333-338.

38. Carretta MD, Alarcon P, Jara E, Solis L, Hancke JL, Concha II, Hidalgo MA, Burgos RA: Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation. Eur J Pharmacol2009, 602:413-421.

39. 39. Abu-Ghefreh AA, Canatan H, Ezeamuzie CI: In vitro and in vivo anti-inflammatory effects of andrographolide. Int Immunopharmacol 2009, 9:313-318.

40. Xu Y, Chen A, Fry S, Barrow RA, Marshall RL, Mukkur TKS: Modulation of immune response in mice immunized with an inactivated Salmonella vaccine and gavaged with Andrographis paniculata extract or andrographolide. Int Immuno pharmaco l 2007, 7:515-5238.

41. Thai Herbal Pharmacopoeia. Vol. 1. 1995. Bangkok, Prachachon Co.

42. Manual for cultivation, production and utilization of herbal medicines in primary healthcare. Nonthaburi, Department of Medical Sciences, Ministry of Public Health (1990).

Received on 17.08.2018 Modified on 20.09.2018

Res. J. Pharmacology & Pharmacodynamics.2018; 10(4): 166-170.

DOI: 10.5958/2321-5836.2018.00031.9

Review Literature: Andrographis paniculata