ORIGINAL ARTICLE Acute and subacute toxicity study of andrographolide bioactive in rodents: Evidence for the medicinal use as an alternative medicine Chellampillai Bothiraja & Atmaram P. Pawar & Vikas S. Shende & Prajakta P. Joshi Received: 4 April 2012 / Accepted: 12 June 2012 #Springer-Verlag London Limited 2012 Abstract Andrographolide, a diterpene bioactive of Androg- raphis paniculata (Acanthaceae family), has long been used in India and China as a complimentary medicine. Yet, there is no detailed toxicological information to guarantee its safe use. In the present study, acute and subacute toxicity of androgra- pholide was assessed via oral route on rodents. In acute toxicity tests, mice (n 0 6/group/sex) received andrographolide at oral doses of 1, 2, 3, 4, and 5 g/kg, whereas in subacute acute tests Wistar rats (n 0 6/group/sex) received 250 and 500 mg/kg for 21 consecutive days. Hematological, biochem- ical, and histological analysis were performed in all animals. No death or hazardous signs were observed from acute toxic- ity study indicating that the LD 50 of andrographolide by oral treatment was greater than 5 g/kg body weight in both male and female mice. No significant changes in body weight gain, food intake, behavior, mortality, hematological, bio- chemical, vital organ weight, and histopathology were ob- served from subacute toxicity study. However, a significant increase in white blood corpuscle (WBC) (7–14 %) and lymphocyte (21–24 %) counts coupled with a reduction in urea (17–24 %) suggested immune-stimulant and renal protective activity of andrographolide. The data support the safety of andrographolide which assure its medicinal use as an alternative medicine. Keywords Andrographolide . Acute toxicity . Subacute toxicity . Rodents Introduction In recent years, there has been evidence for increasing popu- larity of complementary and alternative medicine approaches to health among the Americans. Despite this rapid growth, there is limited evidence about the effectiveness and toxicity of alternative medicine. Much more needs to be done to develop the evidence base for herbals, botanicals, and dietary supplements. Since ancient times, plants have been a source of drugs, but scientific medicine tends to ignore the importance of herbal medicine (Sofowora, 1982). The WHO suggested that effective, locally available plants be used as substitutes for synthetic drugs. Research work on medicinal plants has inten- sified with exchange of information on these plants. Such research will go a long way in the scientific exploration of medicinal plants for the benefit of man and is likely to de- crease the dependence on imported drugs (Amadou, 1998). Andrographolide is a well-known diterpene lactone present in Andrographis paniculata Nees (Acanthaceae family). Al- though popular as ‘king of bitters,’ it has several pharmacolog- ical actions including analgesic, anti-pyretic, anti-inflammatory, hepatoprotectant, anti-viral, anti-cancer, and hypoglycemic ac- tivity (Bothiraja et al., 2009a, b; Shenv et al., 2002; Somenath et al., 2007; Calabrese et al., 2000; Matsuda et al., 1994; Zhang and Tan, 2000). Few toxicological studies have been reported for andrographolide. When it was administered intra- venously at a dose of 10 mg/kg in rabbits, it did not demonstrate C. Bothiraja (*) : P. P. Joshi Department of Phytopharmaceutics, Sharadchandra Pawar College of Pharmacy, Otur, Pune, 412409 Maharashtra, India e-mail: pounbothi@yahoo.com A. P. Pawar Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, 411038 Maharashtra, India V. S. Shende Department of Pharmacology, Sharadchandra Pawar College of Pharmacy, Otur, Pune, 412409 Maharashtra, India Comp Clin Pathol DOI10.1007/s00580-012-1539-x