Bhunimba

Botanical Name: Andrographis paniculata, Acanthaceae

Other Names: Kiratatikta (S), Charayetah, Kiryat, Kalamegh, Kalpath (H), Nilavempu, Shiratkuchi (T), Green Chiretta (E), Chuan xin lian (C)

Botany: Bhunimba is an erect, branched annual, 30-110 cm in height, with four-angled branches. The leaves are simple, glabrous and lanceolate, acute at both ends, up to 8.0 cm long and 2.5 cm broad. The small white flowers are borne in panicles or terminal racemes, giving way to linear-oblong capsules that contain numerous seeds. Bhunimba is found wild and weedy in the plains throughout India and in the undergrowth of forests, from the Himalayan foothills southwards into Sri Lanka. It is also distributed in other locals in Southeast Asia, and has since naturalized in some areas of Central America (Warrier et al 1994, 149; Kirtikar and Basu 1935, 1884-86).

Part used: Whole plant.

Dravyaguna:

• Rasa: katu, tikta

• Vipaka: katu

• Virya: shita

• Karma: dipana, bhedana, krimiaghna, jvaraghna, chedana, raktaprasadana, dahaprashamana, kushtaghna, sandhaniya, lekhana (Warrier et al 1994, 149)

Constituents: Chemical research on Bhunimba leaves has yielded a variety of bitter-tasting diterpene lactones called the andrographolides, as well as the non-bitter neoandrographolide, diterpene dimmers bis-andrograpolides A-D, andrographosterol, andrographane, andrographone, a wax, and two esters containing hydroxyl groups. Bhunimba roots have yielded apigenin-7,4'-di-0-methyl ether, andrographolide, 5-hydroxy-7,8,2',3'-tetramethoxyflavone, a monohydroxy-trimethylflavone, andrographin, a dihydroxy-di-methoxyflavone, panicolin, and ?-sitosterol (Yoganarasimhan 2000, 45; Saxena et al 1998; Matsuda et al 1994).

Medical research:

Upper respiratory tract infection: A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata extract in the treatment of acute upper respiratory tract infections, including sinusitis, over a five day period. 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 test group versus placebo, with a reduction in nasal, sinus, and throat symptoms, and fever, and was well tolerated (Gabrielian et al 2002). Two randomized double-blind, placebo-controlled parallel group clinical trials were performed to investigate the effect of a standardized extract of Andrographis paniculata (Kan jang) in the treatment of uncomplicated upper-respiratory tract infections. Forty-six patients in the pilot study and 179 patients in the phase III study completed the study, taking the medication 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 total symptom diagnosis score showed a significant or highly significant improvement compared to placebo (Melchior et al 2000).

Diabetes: The oral administration of a crude ethanolic extract of Andrographis paniculata was investigated for its anti-diabetic effect in normal and streptozotocin (STZ)-induced diabetic rats. The dosage of the extract at different levels (0.1, 0.2, and 0.4 g/body weight) significantly reduced the fasting serum glucose level in STZ-diabetic rats compared to but not in normal rats, in a dose-dependent manner, similar to metformin (0.5 g/body weight). In a glucose tolerance test, the oral administration of the extract at the same doses suppressed the elevated glucose level in normal and diabetic rats, similar to metformin. In a long-term experiment, the extract (0.4 g/body weight) was compared against metformin (0.5 g/body weight) and placebo, each given twice daily to diabetic rats for 14 days. On day 15, the fasting serum glucose levels and mean food and water intakes were found to be significantly lower in the extract- and metformin-treated groups than in the placebo group. No significant change in insulin level was observed among the 3 groups of diabetic rats, but the activity of hepatic glucose-6-phosphatase (G-6-Pase) was significantly reduced by both Andrographis as well as metformin, the former causing a 49.8% reduction in fasting serum triglyceride levels, compared to 27.7% with metformin (Zhang et al 2002). Researchers investigated the effects of an ethanolic extract of the aerial parts of Andrographis paniculata for its antihyperglycaemic and antioxidant effects in normal and streptozotocin-induced type I diabetic rats treated orally by gavage with a vehicle (distilled water), metformin (500 mg/kg bodyweight) or the Andrographis extract (400 mg/kg bodyweight), twice a day for 14 days. At the end of the 14 day period the extract had significantly increased bodyweight and reduced fasting serum glucose in diabetic rats, but had no similar effect in normal rats. The levels of liver and kidney thiobarbituric acid-reactive substances (TBARS) were significantly lower than the control, while liver glutathione (GSH) concentrations were significantly higher. The extract also significantly decreased kidney TBARS level in normal rats (Zhang and Tan 2000).

Anti-HIV: A clinical trial of andrographolide isolated from Andrographis paniculata was conducted in 13 HIV positive patients and five HIV non-infected healthy volunteers. The objectives were primarily to assess the safety and tolerability of andrographolide, as well as to its effects on plasma virion HIV-1 RNA levels and CD4(+) lymphocyte levels. No subjects used antiretroviral medications during the trial. The 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. Researchers concluded that andrographolide may inhibit HIV-induced cell cycle dysregulation, leading to a rise in CD4(+) lymphocyte levels in HIV-1 infected individuals (Calabrese et al 2000).

Immunomodulatory: The immunomodulatory properties of the diterpene lactone andrographolide and a standardized extract of Andrographis paniculata were investigated for their role on spontaneous and phytohemagglutinin (PHA)-induced proliferation of human peripheral blood lymphocytes and in the production of interferon-? and tumor necrosis factor-?, in vitro. Overall, both andrographolide and Kan Jang demonstrated an in vitro effect on the activation and proliferation of immunocompetent cells as well on the production of key cytokines and immune activation markers, but a more pronounced effect was observed in the herbal extract compared to andrographolide alone (Panossian et al 2002). Pretreatment with andrographolide in rat neutrophils prevented N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion and transmigration of isolated peripheral human neutrophils in a concentration dependent manner. Pretreatment with andrographolide also significantly decreased fMLP-induced up-expression of surface Mac-1 (CD11b/CD18), an essential integrin mediated in neutrophil adhesion and transmigration (Shen et al 2002). A methanol extract of the aerial parts of Andrographis paniculata demonstrated potent cell differentiation-inducing activity on mouse myeloid leukemia (M1) cells (Matsuda et al 1994). An ethanol extract and purified diterpene andrographolides from Andrographis paniculata induced a significant stimulation of antibody and delayed type hypersensitivity response to sheep red blood cells in mice. The purified constituents and ethanol extract also stimulated nonspecific immune response of the animals measured in terms of macrophage migration index phagocytosis of 14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and nonspecific immune response was lower order with andrographolide than with the crude extract (Puri et al 1993).

Hepatic: Pretreatment of mice with the diterpenes andrographolide (I), andrographiside (II) and neoandrographolide (III) isolated from Andrographis paniculata in carbon tetrachloride or tert-butylhydroperoxide-induced hepatotoxicity in mice by for three consecutive days produced a significant reduction in malondialdehyde formation, reduced glutathione (GSH) depletion and enzymatic leakage of glutamic-pyruvate transaminase (GPT) and alkaline phosphatase (AP) (Kapil et al 1993). Andrographolide isolated from Andrographis paniculata showed a significant dose dependent protective activity against paracetamol-induced toxicity on ex vivo preparations of isolated rat hepatocytes, increasing the viability of the hepatocytes and antagonizing the toxic effects of paracetamol on certain enzymes (i.e. GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. Andrographolide was found to be more potent than silymarin (Visen et al 1993). Andrographolide isolated from Andrographis paniculata was shown to produce a significant dose dependent choleretic effect in conscious rats and anaesthetized guinea pigs, evidenced by increases in bile flow, bile salt, and bile acids. Paracetamol-induced decreases in volume and contents of bile was significantly prevented by andrographolide pretreatment, and was found to be more potent than silymarin (Shukla et al 1992). An alcoholic extract of the leaves of Andrographis paniculata was dosed at 300 mg/kg (1/6 of LD₅₀) in experimental carbon tetrachloride-induced liver damage. The extract was shown to be effective in preventing liver damage, evident in positive changes to morphological, biochemical and functional parameters in the damaged livers (Rana and Avadhoot 1991).

Cardiovascular: Researchers investigated andrographolide for its influence on the biosynthesis of eicosanoids and platelet-activating factor (PAF). The results showed that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner, exhibiting a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAIDs) (Amroyan et al 1999). The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA) isolated from Andrographis paniculata was examined for its effects in anaesthetised Sprague-Dawley (SD) rats and isolated rat right atria. In anaesthetised rats, DDA produced a significant decrease in mean arterial blood pressure and heart rate in a dose-dependent manner, acting via adrenoceptors, autonomic ganglia receptor and angiotensin-converting enzyme. In the isolated right atria, DDA caused negative chronotropic action and antagonised isoproterenol-induced positive chronotropic actions in a non-competitive and dose-dependent manner (Zhang et al 1998). An extract of Andrographis paniculata was found to protect the myocardium from ischemic reperfusion injury in experimental animals (Guo et al 1996). The hypotensive activity of an aqueous extract of Andrographis paniculata was studied in hypertensive rats. The extract exhibited a dose-dependent hypotensive effect on systolic blood pressure (SBP), and lowered plasma angiotensin-converting enzyme and lipid peroxidation in the kidneys, as measured by the thiobarbituric acid (TBA) assay (Zhang and Tan 1996).

Urinary: One hundred consecutive cases with renal stones less than 3 cm in size and normal renal function underwent Extracorporeal Shock Wave Lithotripsy (ESWL) from January to March 1994, and out of these, 50 were given Andrographis paniculata tablets (250 mg), 4 tablets thrice daily, 25 were given cotrimoxazole 2 tablets twice daily, and 25 received norfloxacin 200 mg twice daily, all started immediately after ESWL for 5 days. At one month follow-up, pre- and post-ESWL pyuria, hematuria and proteinuria among the Andrographis paniculata group was 84, 58, 72, 40, 52, 22 per cent; the cotrimoxazole group 88, 64, 84, 64, 56, 44 per cent; and the norfloxacin group 92, 56, 72, 40 per cent and 56, 28 per cent respectively. The results indicated that Andrographis presented the best strategy to treat post ESWL urinary tract infection, with no adverse effects (Muangman et al 1995).

Antioxidant: Researchers examined the suppressive effects of Andrographis paniculata on nitric oxide (NO) production in mouse peritoneal macrophages elicited by bacillus Calmette-Guein (BCG) and by lipopolysaccharide (LPS), in vitro and ex vivo. Incubation of BCG-induced macrophages with the methanol extract of A. paniculata reduced LPS stimulated NO production. Isolated diterpene lactones andrographolide and neoandrographolide suppressed NO production in a concentration-dependent manner, but andrographolide did not reduce NO production on oral administration at the same doses, indicating that neoandrographolide, which inhibited NO production both in vitro and ex vivo, may play an important role in A. paniculata’s activity as an anti-inflammatory remedy (Batkhuu et al 2002). The effect a hydroalcohol extract of Andrographis paniculata was examined on drug metabolizing enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the liver of Swiss albino mice over a 14 day period, 50 or 100 mg/kg twice daily. Overall, researchers found that Andrographis demonstrated a chemopreventive effect against chemotoxicity including carcinogenicity, with increases in the levels of acid soluble sulphydryl (-SH) content, cytochrome P450, cytochrome P450 reductase, cytochrome b5 reductase, GST, DTD and SOD, catalase, glutathione peroxidase and glutathione reductase (GR), as well as significant decreases in the activity of LDH and malondialdehyde (MDA) formation (Singh et al 2001). Andrographolide was demonstrated to prevent phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion by rat neutrophils, indicating an anti-inflammatory property (Shen et al 2000). Experimentally-induced atherosclerosis in rabbits were assessed for the effect of an Andrographis paniculata extract upon nitric oxide (NO), endothelin (ET), cyclic guanosine monophosphate (cGMP), lipid peroxide (LPO) and superoxide dismutase (SOD) levels. The extract was shown to increase the levels of NO, cGMP and SOD increased, while LPO and ET were decreased (Wang et al 1997).

Antispasmodic: The effect of an Andrographis paniculata extract was examined for its relaxing effects in the rat uterus pretreated with estradiol and incubated in Ca²⁺-free Jalon's solution and stimulated with KCl in order to produce depolarization of the membrane. Treatment with Andrographis produced a blockade of voltage operated calcium channels, inhibiting the entry of Ca²⁺ from the external medium (Burgos et al 2001).

Antimalarial: In vitro and in vivo studies determined that an extract of Andrographis paniculata have considerable antimalarial effects (Najib et al 1999).

Toxicity: None data found for oral doses. The effect of a powdered extract of Andrographis paniculata leaves was determined to have no effect on blood progesterone in pregnant rats (Panossian et al 1999).

Indications: Dyspepsia, bilious colic, hepatic sluggishness, diarrhea, dysentery, intestinal parasites, hemorrhoids, fever, upper respiratory tract infection, cough, bronchitis, pruritis, inflammatory skin conditions, leprosy, intense thirst, burning sensations, wounds, ulcers, acute and chronic malaria.

Contraindications: Vatakopa.

Medicinal uses: Bhunimba (‘ground nimba’) derives its name from Nimba, the leaves of Azadirachta indica, an intensely bitter remedy that is used primarily to treat Paittic disorders. Thus Bhunimba finds application in a similar range of conditions as Nimba. It is considered synonymous with Kiratatikta (Swertia chirata) in its actions, and is used to treat sannipatta jvara, a type of feverish condition in which all three doshas are pathogenic. It is also used for more straight-forward Paittic conditions such as daha (burning sensation), jvara (fever), ulcers, and trishna (extreme thirst), as well Kaphaja conditions such as kasa (cough, bronchitis), svasa (asthma), and shotha (edema). Thus Bhunimba combines its profoundly bitter, cooling and anti-inflammatory properties with the activity of lekhana, which dries up excessive moisture in the body. Bhunimba has proved to be an important remedy in hepatic dysfunction, and given its antiviral properties, constitutes an exceptionally important remedy in viral hepatitis, as well as other forms of hepatitis induced by drugs such as acetaminophen, or accidental mushroom poisoning. Kirtikar and Basu state that the fresh juice can be extracted and taken alone or with the powders of Ela (Elettaria cardamomum), Tvak (Cinnamomum verum bark), or Lavangaha (Syzygium aromaticum fruit) in the treatment of poor appetite, colic, flatulence and diarrhea, and as a treatment for intestinal parasites (1935, 1885). Such formulations that have dipanapachana components guard against Vata aggravation. In the treatment of malabsorption, abdominal enlargement, jaundice and diarrhea the Chakradatta recommends Bhunimbadya churna, comprised of one part each Bhunimba, Katuka, Trikatu, Musta, and Indrayava (Holarrhena antidysenterica seed), two parts Chitraka and sixteen parts Kutaja (Sharma 2002, 65). Bhunimba is a popular remedy to strengthen the body during influenza epidemics or cold and flu season, to keep the immune system strong. In Chinese medicine Bhunimba is combined with Isatis tinctoria and Taraxacum officinalis in the patent formula Chuan Xin Lian, which is used for the acute onset of colds and flus, especially with fever, sore throat, and lymphadenopathy. Nadakrni reports success with the use of Bhunimba in treatment of malaria, in which it was considered “superior to quinine” (1954, 102). The potent cooling and antiinflammatory properties of Bhunimba have long made it an important remedy in snake and insect bites in both Ayurvedic and Chinese medicine.

Dosage:

• Churna: dried leaves, 2-3 g b.i.d.-t.i.d.
• Phanta: dried leaves, 1:4, 30-60 mL b.i.d.-t.i.d.
• Tincture: dried leaves, 1:4, 50%; 1-3 mL b.i.d.-t.i.d.