INTRODUCTION
Andrographis paniculata, often known as King of Bitters or kalmegh, is an annual, branching, upright attractive herb that grows to a height of half to one meter. It is endemic to peninsular India and Sri Lanka, as well as Southeast Asia, China, the United States, the West Indies, and Christmas Island. It is frequently farmed due to its well-known medicinal benefits and its ability to thrive in a variety of soil types. The plant’s aerial portions and roots have long been utilized in traditional eastern and ayurveda medicine to cure a variety of ailments.
Andrographis paniculata Wall (family Acanthaceae) is a popular medicinal plant that has been used for centuries in Asia, America, and Africa to treat a variety of diseases including cancer, diabetes, high blood pressure, ulcers, leprosy, bronchitis, skin disorders, flatulence, colic, influenza, dysentery, dyspepsia, and malaria. It has a number of photochemical components with unusual biological characteristics. The plant contains diterpenes, flavonoids, xanthones, and other unidentified chemicals. Antimicrobial, cytotoxic, anti-protozoan, anti-inflammatory, anti-oxidant, immunostimulant, anti-diabetic, anti-infective, anti-angiogenic, hepato-renal protective, sex hormone/sexual function modulation, liver enzymes modulation, insecticidal, and toxicity activities of the plant’s extract and pure compounds have been reported.
Phytochemistry
The aerial portions and roots of A. paniculata contain a variety of chemicals that are frequently utilized to extract the active ingredients. Chemical content varies due to a variety of factors such as geographic area, harvest season, and processing method. The separation of different plant metabolites has resulted from phytochemical investigations of A. paniculata. The terpenoids (entalabdane diterpene lactones) are notable among these metabolites since they account for a substantial percentage of its components and therapeutic action. Flavonoids (flavones), xanthones, polyphenols, and trace and macro elements are among the other chemicals that have been identified.
Andrographis is used in a variety of ways
1.Medical applications
The aerial parts, roots, and entire plant of A. paniculata have been used as traditional medicine in Asia for millennia to cure a variety of illnesses. Traditional medical practitioners have used it to treat stomach pains, inflammation, pyrexia, and intermittent fevers. The whole plant has been used to treat dyspepsia, influenza, diarrhoea, malaria, and respiratory infections, as well as as an antidote for snake bites and deadly stings from various insects. Infectious illness, fever-causing disorders, colic discomfort, lack of appetite, irregular stools, and diarrhoea are all treated with the leaf extract.
2.Antimicrobial activity
Aqueous extract, andrographolides, and arabinogalactan proteins isolated from the dried herb of Andrographis paniculata were evaluated for antimicrobial activity. The aqueous extract and arabinogalactan proteins were shown to exhibit antibacterial action against Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa, but andrographolide was found to be active exclusively against B. subtilis
3. Anti-inflammatory/anti-allergic activity
The aqueous extract combined with the methanol extract of the leaves significantly reduced the release of pro-inflammatory mediators (NO, IL-1, and IL-6), inflammatory mediators (PGE2 and TXB2), and allergic mediators (LTB4) induced by lipopolysaccharide, but no inhibition of histamine release was observed. Seven phytochemicals derived from A. paniculata leaves were tested for anti-inflammatory and anti-allergic activity in vitro: andrographolide, neoandrographolide, iso andrographolide, andrograpanin, 7-O-methylwogonin, 14-deoxy-11,12-didehydro andrographolide, and skullcap flavone. The findings revealed that andrographolide, iso andrographolide, 7-O-methylwogonin, and skullcap flavone-1 substantially reduced the production of inflammatory mediators NO and PGE2 from cultured macrophages challenged with lipopolysaccharide (LPS).
4.Anti-oxidant activity
The antioxidant activity of andrographolide and aqueous extract of A. paniculata herbs was tested on nicotine-induced oxidative stress in the liver, kidney, heart, lungs, and spleen, and the results showed that intraperitoneal administration of andro (25 mg/kg) and Aphanamixis polystachya (25 mg/kg) for 7 days significantly reduced lipid peroxidation and increased antioxidant activity. Methanol and aqueous extracts of A. paniculata leaves from various sites, as well as andrographolide and 14-deoxy-11, 12-didehydro andrographolide, were shown to prevent lipid peroxidation and had free radical scavenging properties against DPPH.
5.Immunostimulant activity
Purified diterpenes- andrographolide and neoandrographolide and ethanol extract of the fresh plant elicited substantial antibody stimulation.
Andrographis in cancer
Andrographis paniculata extracts have proved to be effective against a variety of illnesses, including cancer. Lactone and diterpene are the most active biomolecules in Andrographis paniculata. Andrographolide and its equivalents have long been used to prevent a variety of illnesses. Andrographolides have been found to have anti-inflammatory and cancer-fighting properties. It showed promise as a chemopreventive drug by inhibiting the NF-kappaB, PI3K/AKT, and other kinase pathways, as well as causing apoptosis in cancer cells. Through the production of anti-apoptotic proteins such as Bax, p53, and activated caspases, andrographolide triggered both intrinsic and extrinsic death pathways in several cancer cells. Andrographolide has been used successfully in cancer treatment as an anticancer medication. Human breast, prostate, and hepatoma cancers were all suppressed by andrographolide. More clinical and biological research on andrographolide and analogues in cancer chemoprevention is needed. When combined with other chemotherapeutic drugs, andrographolide might be a powerful anticancer agent.
Mechanism of Action
Andrographolides are diterpenoid lactones that are the active components of andrographis. They have anti-inflammatory properties via decreasing the generation of nitric oxide and the expression of cyclooxygenase-2. Andrographis enhanced mRNA expression of P450 subfamily members CYP1A1 and CYP1A2 in a concentration-dependent manner. Andrographis extract has been shown in previous research to have a calcium channel inhibitory effect, which can promote smooth muscle relaxation, lower blood pressure and heart rate, and calm the uterus. It also inhibited thrombin and platelet activating factor, which had antiplatelet effects. Andrographis extract was found to neutralize snake venom when administered orally to mice. Furthermore, andrographolides prevent HIV-induced cell cycle dysregulation and increased CD4+ lymphocyte numbers in HIV-1 patients.
Preclinical investigations have shown that andrographolides have anticancer properties. TLR4/NF-kappaB signalling pathway suppression may be involved in activity against multiple myeloma cells. The reversal of 5-FU resistance in human colorectal cancer cells was related to increased BAX expression. In addition, mRNA and matrix metalloproteinase (MMP)-7 protein levels were suppressed, and MMP-2 activity was detected, which prevented migration and invasion. In human prostate cancer cells, IL-6 expression and IL-6-mediated signalling are inhibited. Andrographolides inhibited MMP-7 expression and suppressed the PI3K/Akt/AP-1 signalling pathway in non-small cell lung cancer cells, reducing invasiveness. Induction of c-Jun N-terminal kinase and caspase activation caused apoptosis in human hepatoma cells. Inhibition of E-selection expression was linked to decreased adherence of gastric cancer cells to endothelial tissue. The stimulation of cytotoxic T-lymphocyte production by IL-2 and IFN-gamma release may also inhibit tumour cell proliferation. Andrographolides significantly increased doxorubicin-induced cell death in numerous human cancer cell lines, mostly through suppressing JAK-STAT.
