ANDROGRAPHIS

BACKGROUND

Ingredient Type: Botanical, Herb, Extract

Also Known As: Green chiretta, Andrographis paniculata, Andrographolide, Kalmegh

Andrographis, also commonly referred to as “King of Bitters,” is native to Southern and Southeast Asia, more specifically India and Sri Lanka. The plant is an herb that grows to 12”-43” in height and is extremely bitter.

TRADITIONAL USES

Andrographis has been used in various cultures as a bitter tonic to promote better digestion and regularity along with immune system support. In some parts of the world, this herb has been used to support cancer patients, although there is no current evidence of a cure or prevention due to the use of Andrographis (1).

In traditional medicine or ayurvedic medicine, Andrographis has been used to help treat jaundice as noted in this ethnomedicinal study, which is aimed to classify and categorize medicinal plants effective for the treatment of jaundice (2).  Traditionally in Indian and Chinese herbal medicine, Andrographis is also used to treat upper respiratory infections (3,4).

WHAT DOES SCIENCE TELL US?

Andrographis Might Support Immune Health:

With Andrographis being know to modulate the immune system, a study was conducted to investigate the immunomodulatory effects of andrographolide, a compound from the stem and leaf of Andrographis, on both the innate and adaptive immune responses. The andrographide was used to modulate LPS-induced classical activated or IL-4-induced alternative activated (M2) macrophages in vitro and humoral immune responses to HBsAg in vivo. To assess the effectiveness, cytokine expression was measured by real-time PCR, IL-12/IL-10 levels were measured, and surface antigen expression was additionally evaluated. Based on the yielded results, andrographide was able to modulate the innate and adaptive immune responses through macrophage phenotypic regulation and Ag-specific antibody production (5).

Another study assessed an inhalable version of andrographolide (AG) in the treatment of Staphylococcus aureus Pneumonia via immune response regulation. The administration of AG-B-CD was identified with X-ray diffraction and FT-IR. Although oral therapy of AG and AG-B-CD showed little anti-S. aureus activity in vitro; pulmonary delivery of AG, AG-B-CD or penicillin, however, had significant anti- S. aureus pneumonia effects. This delivery system led to bacterial inhibition and inflammation alleviation through immune response regulation. A higher anti-pneumonia activity, however, was noted with AG-B-CD than that of AG. Based on this study, it has been concluded that an inhalable AG-B-CD may be a promising antibacterial and anti-inflammatory alternative for the treatment of S. aureus pneumonia (6).

In another study, a major component of Andrographis, 14-Deoxy-11,12-didehydroandrographolide (DAP), was used at a non-toxic concentration of 1000 mg/kg/day on mice challenged with an influenza virus (H5N1). In this study, the DAP was noted to alleviate any lung histopathology along with inhibiting proinflammatory cytokine and chemokine expression. From the results, it was concluded that DAP might be a promising component of Andrographis that can be used in the reduction of proinflammatory mediators (7).

An alternate study assesses a major bioactive labdane diterpenoid isolated component from Andrographis paniculata, assessing its protective effects against cigarette smoke-induced lung injury. Human alveolar epithelial tissue, A549 cells, were exposed to cigarette smoke extract with and without the andrographolide pretreatment. The following biomarkers were assessed to determine mechanism and effectiveness: glutathione levels, nuclear factor-kappaB (NK-kB) activation, proinflammatory cytokine production, and miR-218 expression. Compared to the control, non-treatment group, the treatment group was found to have significantly restored glutathione levels signifying supportive immune system modulation. From the results, it was recognized that andrographolide mitigates cigarette smoke extract-induced inflammatory responses in A549 cells. Therefore, andrographolide has potential preventative benefits to cigarette smoke-induced inflammatory lung disease (14).

Andrographis Possibly Supports Healthy Cells Growth:

In one study, the botanical compound andrographolide extract was utilized to induce cell death of prostate cancer PC-3 cells in vitro. Upon testing, the andrographolide showed selective cytotoxicity to the PC-3 cells. Upon assessment of the cells post-application, the following evidence was noted after a 4-hour treatment: cell shrinkage, surface microvilli loss, chromatin condensation/fragmentation. Under an electron microscope, apoptotic body formation was noted following an 8-hour treatment application. Caspase-3 & 8 activation was also noted using immunocytochemistry. The researchers concluded from the observed data that andrographolide-induced cell death was achieved via the apoptotic pathway, via the activation of an extrinsic caspase cascade (8).

In another study, the cytotoxicity of ethanol extract of Andrographis paniculata and its main components were studied in vitro against various cancer cells. Three components of the plant were studied: Andrographolide, Deoxyandrographolide, and Neoandrographolide. The results were assessed via laser confocal microscopy and gel electrophoresis, which noted chromosomal DNA fragments indicative of apoptotic activity. The andrographolide form was noted to exhibit the highest degree of cytotoxicity. From this study, it was assessed that the A paniculata was significantly noted to be a growth inhibitor to human acute myeloid leukemic HL-60 cells(10).

Andrographis Possibly Supports Cardiovascular Health:

According to one study, “Andrographolide (ANDR), a botanical compound, has potent cardio-protective effects due to its ability to inhibit mitogen-activated protein kinases (MAPKs); ANDR has also been shown to inhibit inflammation and apoptosis, which are factors related to cardiac hypertrophy. (11)”

In this second study, the effects of ANDR on cardiac hypertrophy and MAPKs activation. The rat subjects were subject to aortic banding (AB) with and without ANDR administration. To measure the efficacy, cardiac function was assessed by echocardiography and hemodynamic parameters. The results noted decreased cardiac dysfunction and attenuated cardiac hypertrophy and fibrosis following seven weeks of ADR administration. The ANDR also significantly inhibited MAPKs activation in subjects’ hearts and cardiomyocytes. The results confirmed ANDR’s efficacy, as noted by its protective nature for pathological cardiac hypertrophy (11).

Andrographis Possibly Decreases Inflammatory Responses:

In one randomized, double-blind, placebo-controlled trial, Andrographis paniculata was studied in 244 adults to see its effect on mild to moderate ulcerative colitis. According to studies, A. paniculata is known to have in vitro inhibitory activity against immune modulation, thereby assisting in helping decrease the inflammatory response. Participants in the test groups were administered either 1,200 mg or 1,800 mg of the extract (HMPL-004) or the placebo for eight weeks. The following was observed: 45 of the participants who received 1,200 mg and 1,800 mg daily were in clinical response at week eight compared to the placebo group. Thirty-four of the participants of this group were in clinical remission at week eight compared with 25% in the placebo group. Adverse events did, however, occur in 53% of the test group as well as 60% in the placebo group. It was concluded from this study that patients with mild to moderately active ulcerative colitis could potentially benefit from A. paniculata extract at a dose of 1,800 mg per day (15).

In another study, the Andrographis paniculata extract (SHA-10) was studied to measure the effectiveness in reducing the prevalence and intensity of signs and symptoms associated with the common cold. This double-blind study consisted of 158 adult participants of both sexes. The test group received 1,200 mg/day while the placebo group did not any during the 5-day duration. Measurements were taken on days 0, 2, and 4 post-administration. The self-reported measures were: headache, tiredness, earache, sleeplessness, sore throat, nasal secretion, phlegm, frequency, and intensity of cough. On day two, there was a significant decrease in about half of the observed signs and symptoms with the A. paniculata test group as compared with the placebo group. As of day 4, there was a significant decrease in all the signs and symptoms A. paniculata test group. From this study, it was concluded that A. paniculata extract (SHS-10) is effective in reducing the prevalence and intensity of signs and symptoms associated with the common cold Additionally, no adverse effects were associated with the consumption of A. paniculata in this study (16).

SAFETY

According to the Australian Government’s Therapeutic Goods Administration’s (TGA) Gov., there is not enough clinical exposure and research to provide a comprehensive safety profile on Andrographis paniculata. Their recommendations are purely from safety issues in published literature and form international pharmacovigilance activities.

Interactions:

Andrographis seems to decrease blood pressure. Taking andrographis along with medications for high blood pressure might cause your blood pressure to go too low.

Andrographis increases the immune system. By increasing the immune system, andrographis might decrease the effectiveness of medications that decrease the immune system.

Andrographis might slow blood clotting. Taking andrographis along with medications that also slow clotting might increase the chances of bruising and bleeding (17).

Side-Effects:

Of TGAs review of products containing A. paniculata, 165 ADR cases were reported from products containing A. paniculata; 38 of these cases were associated with anaphylactic reactions. In 36 of the 38 cases, A. paniculata was part of multi-ingredient formulations. However, 5 of the noted 38 cases pointed to A. paniculata as being the sole active ingredient related to the anaphylaxis (12).

The remaining 72 cases represented with a type of allergic reaction associated with one or more of the following symptoms: hypersensitivity, dyspnea, urticaria, pruritis, paranesthesia, rash, periorbital oedema, lip swelling, face oedema, angioedema, erythema, auricular swelling, throat tightness, wheezing, palpitations, hyperhidrosis, increased respiratory rate, hypoxia, erythematous rash or pruritic rash. Of the 72 cases, 65 of the cases the medicine contained A. paniculata was the sole suspected medicine where 11 of the cases that contained A. paniculata was considered the sole active ingredient. In conclusion, based on TGAs assessment, in the absence of allergy history for each repot, no conclusion can be drawn about the potential likelihood of an allergic response in individuals with a history of allergy, anaphylaxis or asthma (12).

Another study assessed Andrographis paniculata for its potential toxicity. According to the study, upon assessing numerous toxicity evaluations of various extracts, metabolites, and other components of the plant, there was no significant acute toxicity in the experimented animals (13).

Lastly, considering the nature of Andrographis paniculata to elicit a strong immune response, especially when an illness is present or some sort of auto-immune condition (multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, etc.), it is not recommended to use A. paniculata.

REFERENCES

1. Andrographis. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/andrographis. Accessed 27 June 2019.
2. Tewari D, Mocan A, Parvanov ED, Sah AN, Nabavi SM, Huminiecki L, Ma ZF, et al. Ethnopharmacological Approaches for Therapy of Jaundice: Part I. Front Pharmacol. 2017;8:518.
3. Hu XY, Wu RH, Logue M, Blondel C, Lai LY, Stuart B, Flower A, Fei YT, Moore M, Shepherd J, Liu JP. Andrographis paniculata (Chuan Xin Lian) for Symptomatic Relief of Acute Respiratory Tract Infections in Adults and Children: A Systematic Review and Meta-Analysis. PLOS One. 2017;12(8): e0181780.
4. Mishra SK, Sangwan NS, Neelam S, Sangwan RS. Andrographis Paniculata (Kalmegh): A Review. Pharmacognosy Reviews. 2007;1(2):283-98.
5. Wang W, Wang J, Dong SF, et al. Immunomodulatory Activity of Andrographolide on Macrophage Activation and Specific Antibody Response. Acta Pharmacol Sin. 2010; 31(2):191-201.
6. Zhang T, Zhu L, Li M, Hu Y, Zhang E, et al. Inhalable Andrographolide-B-Cyclodextrin Inclusion Complexes for Treatment of Staphylococcus aureus Pneumonia by Regulating Immune Responses. Mol. Pharmaceutics. 2017;14(5):1718-1725.
7. Cai W, Chen S, Li Y, et al. 14-Deoxy-11,12-didehydroandrographolide Attenuates Excessive Inflammatory responses and Protects Mice Lethally Challenged with Highly Pathogenic A(H5N1) Influenza Viruses. Antiviral Res. 2016; 133:95-105.
8. Kim TG, Hwi KK, Hung CS. Morphological and Biochemical Changes of Andrographolide-Induced Cell Death in Human Prostatic Adenocarcinoma PC-3 Cells. In Vivo. 2005;19(3): 551-557.
9. Yusuf AL, Goh YM, Samsudin AA, Alimon AR, Sazili AQ. Growth Performance, Carcass Characteristics and Meat Yield of Boer Goats Fed Diets Containing Leaves or Whole Parts of Andrographis paniculata. Asian-Australasian Journal of Animal Sciences. 2014;2(4):503-510.
10. Cheung HY, Cheung SH, Li J, et al. Andrographolide Isolated from Andrographis paniculata Induces Cell Cycle Arrest and Mitochondrial-Mediated Apoptosis in Human Leukemic HL-60 Cells. Pharmacology. 2005;71(12):1106-11. doi:10.1055/s-2005-873128.
11. Andrographis: Health Benefits, Uses, Side Effects, Dosage & Interactions. https://www.rxlist.com/andrographis/supplements.htm Accessed 28 June 2019.
12. Safety Review of Andrographis paniculata and Anaphylactic/Allergic Reactions. https://www.tga.gov.au/sites/default/files/safety-review-andrographis.docx Accessed 28 June 2019.
13. Okhuarobo A, Falodun JE, Erharuyi O, et al. Harnessing the Medicinal Properties of Andrographis paniculata for Diseases and Beyond: A Review of its Phytochemistry and Pharmacology. Asian Pac J Trop Dis. 2014; 4(3):213-222. DOI: 10.1016/S2222-1808(14)60509-0
14. Li YJ, Yu CH, Li JB, Wu XY. Andrographolide Antagonizes Cigarette Smoke Extract-Induced Inflammatory Response and Oxidative Stress in Human Alveolar Epithelial A549 Cells Through Induction of MicroRNA-218. Experimental Lung Research. 2013;39(10): 463-471.
15. Sandborn WJ, Targan SR, Byers VS, Rutty DA, Mu H, Zhang X, Tang T. Andrographis paniculata Extract (HMPL-004) for Active Ulcerative Colitis. American Journal of Gastroenterology. 2013;108(1): 90-98. doi: 10.1038/ajg.2012.340
16. Caceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. Use of Visual Analogue Scale Measurements (VAS) to Assess the Effectiveness of Standardized Andrographis paniculata Extract SHA-10 in Reducing the Symptoms of Common Cold. A Randomized Double Blind-Placebo Study. Phytomedicine. 1999;6(4): 217-223. DOI:10.1016/S0944-7113(99)80012-9
17. Andrographis. https://www.webmd.com/vitamins/ai/ingredientmono-973/andrographis Accessed 24 July 2020.