Andrographis

Generic name: Andrographis Paniculata (Burm.f.) Wall. Ex Nees
Brand names: Alui, Bhui-neem, Bhunimba, Chuan Xin Lian, Chuanxinlian, Creat, Green Chireta, Kalmegh, Kalmegha, King Of Bitters, Kirayat, Mahatita, Nemone Chinensi, Sam Biloto, Yavatikta

Usage of Andrographis

Alcohol use disorder

Animal data

Both the extract of A. paniculata and andrographolide reduced alcohol-seeking behavior in rats genetically prone to prefer alcohol (P<0.001 for each). The extract also reduced cue-induced but not yohimbine-induced alcohol seeking.(Stopponi 2021)

Anti-inflammatory effects

Animal data

In several cellular systems, andrographolide has demonstrated anti-inflammatory effects, including prevention of phorbol ester–induced reactive oxygen species and N-formyl-methionyl-leucyl-phenylalanine–induced adhesion in rat neutrophils,(Hidalgo 2005, Shen 2000) inhibition of tumor necrosis factor–induced upregulation of intercellular adhesion molecule expression, monocyte adhesion,(Habtemariam 1998)) and activation of protein kinase pathways.(Chen 2004) In a rat model of gout, both andrographolide and an alcoholic extract of andrographis demonstrated extensive reductions in many inflammatory cytokines, as well as reduced uric acid levels.(Rahmi 2022)

Clinical data

Two randomized, double-blind clinical studies in patients with ulcerative colitis (N=120 and N=224) suggest extracts of andrographis may be as effective as mesalamine. Dosages of 1,200 mg or 1,800 mg of A. paniculata extract daily (in 3 divided doses) for 8 weeks were used in the studies.(Sandborn 2013, Tang 2011)

In 60 patients with rheumatoid arthritis, andrographolides 30 mg taken 3 times daily over 14 weeks resulted in improved rheumatoid symptoms of swelling and tenderness; reductions in rheumatoid factor and other indices were also associated with treatment compared with placebo.(Burgos 2009)

A clinical study assessing the effects of twice-daily A. paniculata 170 mg on relapse rate and fatigue in 25 patients with multiple sclerosis reported reductions in fatigue.(Bertoglio 2016)

Antimicrobial and antiviral effects

Animal and in vitro data

Extracts of andrographis and andrographolide derivatives have shown modest activity in vitro against HIV.(Basak 1999, Chang 1988, Otake 1995, Reddy 2005, Yao 1992) Cell culture studies of andrographolide have also demonstrated effects against 2 viruses in the Flaviviridae family: dengue virus (serotypes 2 and 4)(Panraksa 2017) and Japanese encephalitis virus.(Bhosale 2021) The ethanolic extract of A. paniculata (7.9% andrographolide) and its major constituent andrographolide demonstrated inhibitory activity against SARS-CoV-2 virus replication in human lung epithelial cells in a dose-dependent manner in vitro. Respective IC50 values for A. paniculata and andrographolide were 0.036 mcg/mL and 0.034 mcM using plaque assays that measure infectivity of virions released from the host cell. In contrast, IC50 values were higher using assay methods that require expression of specific antibodies. This difference demonstrated that A. paniculata and andrographolide interfere more with the production of infectious viral progeny than the early phase of viral replication. The A. paniculata extract demonstrated no cytotoxicity in cell lines of major organs (ie, lung, liver, brain, kidney, intestines); however, andrographolide demonstrated a narrow safety index in brain cells. Low bioavailability of andrographolide was also noted as a potential limitation for clinical applications.(Sa-Ngiamsuntorn 2021)

Antimalarial activity has also been noted during screening of andrographis extracts.(Misra 1992, Najib 1999, Siti Najila 2002)

The extract of A. paniculata blocked Escherichia coli enterotoxin–induced secretion in rabbit and guinea pig models of diarrhea.(Gupta 1993) Andrographolide and 3 other related diterpenes were responsible for this action.(Gupta 1990) Results from other in vitro experiments evaluating the action of andrographolide and A. paniculata leaf extracts on E. coli are conflicting.(Singha 2003, Voravuthikunchai 2006)

Clinical data

A phase 1 study of andrographolide use in patients who were HIV positive showed no effect on viral replication after 6 weeks, despite increased CD4+ counts.(Calabrese 2000)

Clinical trials have demonstrated beneficial results regarding respiratory infections, but methodology used is often of poor quality.(Gabrielian 2002, Hancke 1995, Spasov 2004) A clinical study evaluated the effect of A. paniculata extract 200 mg/day for 5 days on 9 self-evaluated symptoms (cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue, and sleep disturbance) in uncomplicated upper respiratory tract infection (N=223), with results favoring the study preparation over placebo.(Saxena 2010) A retrospective study of patients hospitalized with COVID-19 in Thailand found no difference in pneumonia rates for treatment with andrographolide 180 mg for 5 days compared with conventional therapy.(Tanwettiyanont 2022)

Cancer

Animal and in vitro data

In animal and in vitro experiments using human cancer cell lines to investigate the potential anticancer effects of A. paniculata, andrographolide was responsible for the observed beneficial effects rather than other diterpenes.(Kumar 2004, Mishra 2015, Nanduri 2004, Zhou 2006) Various mechanisms of action have been proposed, including enhancement of chemokine activity, inhibition of tumor-specific angiogenesis affecting cell cycle progression, and induction of apoptosis.(Ji 2005, Kumar 2004, Nanduri 2004, Sheeja 2007, Zhou 2006) Cancer cell lines investigated included prostate, breast, cervical, colon, hepatoma, melanoma, and lymphocytic leukemia. Researchers are focusing on synthesizing compounds based on andrographolide to improve selectivity and potency.(Jada 2006, Nanduri 2004)

Caution is recommended due to the potential for andrographolide-enhanced SDF-1-chemokine activity, which might induce tumor cell metastasis.(Ji 2005) A. paniculata extract has also induced cell differentiation in mouse myeloid leukemia cells.(Matsuda 1994)

CNS effects

Animal and experimental data

In silico simulations identified 3 compounds from A. paniculata with high binding affinity for 3 beta-amyloid target enzymes (ie, human acetylcholinesterase [AChE], butylcholinesterase [BChE], and beta-secretase-1 [BACE-1]) and, therefore, might serve as potential anti-amyloid/Alzheimer agents. Subsequent in vitro studies demonstrated one of the compounds (3,4-di-o-caffeoylquinic acid) to have better mean IC50 values against both AChE (2.14 mcM) and BChE (1.44 mcM) than the positive control physostigmine (3.39 mcM and 2.88 mcM, respectively). Similar cholinesterase inhibition was observed with the second compound (7-o-methylwogonin), which had mean IC50 values for AChE (2.46 mcM) and BChE (1.46 mcM) that were also lower than physostigmine, while the third compound (apigenin) demonstrated better inhibition of BChE (1.97 mcM) than AChE (3.42 mcM). Only 7-o-methylwogonin was observed to have comparable inhibition of BACE-1 as the positive control (quercetin); both demonstrated an IC50 of 2.91 mcM, while the other 2 compounds were slightly less active against BACE-1.(Panche 2019) These effects were supported by a subsequent rat dementia (amnestic) model in which an aqueous extract of A. paniculata leaves significantly improved memory and cognitive function (P<0.05) compared with controls. Pretreatment with the extract prevented the increases in AChE, BChE, and MAO in the hippocampus induced by scopolamine.(Adedayo 2021)

Contraception

Animal data

Male rats that consumed an A. paniculata leaf decoction daily for 8 weeks exhibited dose-dependent decreases in sperm counts, motility, and viability compared with controls. Results were marginal except in the high-dose group (1,000 mg/kg), for which decreases were significant compared with control (P<0.05). The high-dose group demonstrated normal seminiferous tubules with complete maturation and presence of spermatozoa; however, fibrosis in the lumen and degenerated germ cells were observed. Significant reductions in Leydig cell mass (steroidogenesis), mean seminiferous tubular diameter, and spermatogenic index (spermatogenesis) were also evident compared with controls. The mechanism appeared to be related to dose-dependent reductions in testosterone and increases in follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as well as improved redox and inflammatory processes.(Ogundola 2021)

Hepatoprotective effects

Animal data

The extract of A. paniculata has demonstrated hepatoprotective activity in animal studies.(Kapil 1993, Trivedi 2000, Visen 1993) Hepatic drug-metabolizing enzymes were elevated in one animal experiment.(Visen 1993) However, it should be noted that in one clinical trial evaluating use of andrographolide, elevated liver enzymes were reported.(Calabrese 2000)

Hypertriglyceridemia

Clinical data

In a clinical study of patients with modest hypertriglyceridemia (N=60), administration of A. paniculata extract (andrographolide) 120 mg/day improved serum triglyceride levels.(Phunikhom 2015)

Hypoglycemic effects

Animal data

Extracts of andrographis have demonstrated hypoglycemic action in rats with streptozotocin- and alloxan-induced diabetes, which supports traditional use of the plant in diabetes.(Husen 2004, Reddy 2005, Zhang 2000)

Hypotensive effects

Clinical data

Two older trials explored the possible hypotensive effects of andrographolide/andrographis, but further investigation is needed.(Reyes 2006, Zhang 1999)

Immunostimulant activity

Stimulation of the production of key cytokines and immune activation markers has been investigated as a potential mechanism of andrographolide immunomodulation.(Ji 2005, Ko 2006, Panossian 2002)

Animal data and in vitro data

In one study, both antigen-specific and antigen-nonspecific immune responses in mice were stimulated by andrographolide and an ethanolic extract; the extract was more potent than andrographolide, suggesting that other constituents of the extract were also immunostimulants.(Puri 1993) Inhibition of passive cutaneous anaphylaxis and mast cell stabilization was observed in studies of the purified diterpenes in rats.(Gupta 1998)

Clinical data

In 30 healthy adults enrolled in an open-label, single-arm pilot study, levels of interferon (IFN)-gamma and interleukin 4 (IL-4) were significantly increased while IL-2 was significantly decreased after 30 days of A. paniculata (standardized to at least 33% diterpene lactones and 30% andrographolide) 100 mg twice daily. The primary outcome of change in natural killer cells was not found to be evident; however, a trend for increased total lymphocytes, CD3+ T-cells, and CD3+CD4+ T-helper cells was noted. In the subgroup of patients with baseline lymphocyte counts that ranged from 1,000 to 3,000 cells/mm3 (n=21), the changes in lymphocyte counts were statistically significant compared with baseline. Andrographis was well tolerated with no adverse events reported.(Rajanna 2021)

Insecticidal activity

Experimental data

Repellency activity of an ethanolic extract of A. paniculata leaves was investigated against 5 important mosquito species that are human pathogen vectors in Thailand. Significant activity was observed for most mosquitoes, with high repellency demonstrated against Aedes aegypti (dengue) and moderate activity observed against Anopheles dirus (malaria) and Culex quinquefasciatus (human lymphatic filariasis). Andrographolide and 14-deoxyandrographolide were determined to be the main active compounds.(Sukkanon 2020)

Osteoarthritis

Clinical data

In a double-blind, randomized, controlled study of Asian patients with osteoarthritis of the knee (N=103), twice-daily administration of 150 or 300 mg of a standardized extract of A. paniculata (50% andrographolide) for 3 months significantly reduced pain scores, stiffness, physical function, and total Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score compared with placebo (P<0.0001 for each). Additionally, fatigue and quality of life were significantly improved in the A. paniculata group compared with placebo (P=0.0001 for each).(Hancke 2019)

Renal toxicity

Animal data

Nephroprotective effects of A. paniculata have been demonstrated in animal models of diabetic nephropathy and drug-induced nephrotoxicity.(Hidayat 2021, Sharma 2022) A. paniculata extract not only ameliorated kidney hypertrophy in a diabetic rat model but also significantly improved body weight, fasting blood glucose, urine creatinine, albumin, triglycerides, cholesterol, and advanced glycation end products.(Hidayat 2021) Meanwhile, nephrotoxicity in rats induced by antitubercular drugs was mitigated with a high dose of A. paniculata leaf extract (300 mg/kg), with serum renal function markers (urea, creatinine, uric acid) restored towards normal values.(Sharma 2022)

Andrographis side effects

Research reveals few adverse reactions reported with use of A. paniculata. However, adverse reactions (eg, headache, fatigue, rash, bitter/metallic taste, diarrhea, pruritus, decreased sex drive) during a phase 1 study of andrographolide in patients who were HIV positive and healthy volunteers required interruption of the trial. One participant who was HIV positive experienced an anaphylactic reaction. Adverse reactions became apparent at an andrographolide dose of 10 mg/kg body weight.(Calabrese 2000) In the same trial, elevated liver enzymes were experienced by many subjects. Two cases of urticaria were reported in other trials.(Poolsup 2004) A meta-analysis of trials of andrographis and andrographolide derivatives found that adverse effects, including death, were more frequent with the derivatives, while adverse reactions with andrographis were generally mild to moderate.(Shang 2022)

Before taking Andrographis

Avoid use. Adverse effects, including abortifacient effects, have been documented.(McGuffin 1997)

How to use Andrographis

Limited quality clinical studies exist to provide dosing recommendations.

Immunostimulant

One small study evaluated the immunostimulant effects of A. paniculata (standardized to at least 33% diterpene lactones and 30% andrographolide) 100 mg twice daily for 30 days.(Rajanna 2021)

Osteoarthritis

Twice-daily administration of 150 or 300 mg of a standardized extract of A. paniculata (50% andrographolide) for 3 months was evaluated in patients with osteoarthritis of the knee.(Hancke 2019)

Respiratory tract infection

A clinical study evaluated the effect of A. paniculata extract 200 mg/day for 5 days on symptoms of uncomplicated upper respiratory tract infection.(Saxena 2010)

Ulcerative colitis

A. paniculata extract dosages of 1,200 or 1,800 mg daily (in 3 divided doses) for 8 weeks were used in studies of ulcerative colitis.(Sandborn 2013, Tang 2011)

Warnings

Toxicology studies are limited, but andrographis does not appear to be acutely toxic. Acute lethal doses (median lethal dose) in mice are reported to be more than 40 g/kg for andrographolide.(Calabrese 2000)

Ames, chromosome aberration, and micronucleus in vitro tests on a standardized extract of A. paniculata demonstrated no evidence of mutations or clastogenicity, and no evidence of acute toxicity was observed in the female rats studied.(Chandrasekaran 2009)

Male reproductive toxicity studies have been conducted with andrographis. A subchronic 60-day study in male rats showed no changes in testicular weight, histology, or testosterone levels.(Burgos 1997) However, studies in rats given purified andrographolide for 48 days showed decreases in sperm counts and motility that were linked to disruption of spermatogenesis.(Akbarsha 2000, Hossain 2014)

What other drugs will affect Andrographis

None well documented.

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