Int J Pharm Pharm Sci, Vol 15, Issue 2, 1-7Review Article

A COMPREHENSIVE REVIEW OF KALMEGH'S BIOLOGICAL ACTIVITIES (ANDROGRAPHIS PANICULATA)

ANJU BHATNAGAR*

Department of Chemistry, D. B. S. (P. G.) College Dehradun, India 248001
*Email: dbsanju2014@gmail.com

Received: 30 Oct 2022, Revised and Accepted: 20 Dec 2022

ABSTRAC

Kalmegh is a valuable herb belonging to the family Acanthaceae that has been used traditionally in India and Southeast Asia to cure a variety of illnesses like diabetes, viral hepatitis, high blood pressure, ulcers, and malaria. It has many important bioactive compounds, such as diterpenoids, flavonoids, and polyphenols. The most common and abundant diterpenoid is andrographolide. It cures and prevents several diseases in humans. Andrographis and its extract have been documented for their various medicinal uses. A full bibliographic inquiry was conducted using extensively used scientific databases like Web of Science, research articles, and online as well as offline sources. A goal of the current review is to analyze the Andrographis paniculata's traditional usage, chemical components, and biological activities to highlight, explore, and lay the groundwork for future research.

Keywords: Andrographis paniculata, Bioactive constituents, Pharmacology, Medicinal uses hepatoprotective, Antioxidant activity

© 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
DOI: https://dx.doi.org/10.22159/ijpps.2023v15i2.46705. Journal homepage: https://innovareacademics.in/journals/index.php/ijpps.

INTRODUCTION

Medicinal plants have been integral to man's health and healing since the dawn of human civilization. Despite of significant advancements made in allopathic medicines during the 20th century, both the ancient and contemporary systems of medicine continue to rely heavily on plants as a source of medications. The majority of the world's populations, who reside in underdeveloped nations, rely on traditional medicine and herbal remedies to meet their primary healthcare needs. According to reports, up to 8000 plants can be used in the Ayurvedic, Homeopathic, Siddha, Unani, and Tibetan medical systems [1-3]. One of them is Andrographis paniculata commonly known as ‘King of Bitter’. It generally grows abundantly in Southeast Asia, Sri Lanka, and India. It can increase in height to a maximum of one meter, with small, hairy white to pink blooms and lanceolate leaves. The leaf is the primary therapeutic component, while the entire plant, including the root, is used for a variety of illnesses. In India, it grows in the rainy season, when heat and humidity with lots of sunshine are the ideal climate conditions for the plant.

In India, both tribal and traditional medicine systems make considerable use of Andrographis paniculata as a home treatment for various illnesses. The most utilized component of Andrographis paniculata is the aerial part, and its major bioactive constituents are diterpenoids, flavonoids, and xanthones. In Asia and Europe, whole plants and leaves are utilized as folk remedies for a variety of illnesses. This plant is prescribed to treat several chronic and infectious illnesses, such as sore throats, fever, herpes, and upper respiratory and gastrointestinal infections [4–7].

Ethnobotanical uses

For ages, Asia's traditional healers have used the leaves and roots of Andrographis paniculata to treat a variety of illnesses like fevers, diarrhea, and getting rid of intestinal worms [8]. The plant is used as a liver tonic, blood–purifier, and antidote for snake bites, scorpions, and centipede stings [9, 11]. It is also useful for burning sensations, wounds, skin diseases, and leprosy. Plant powder is used to relieve itching. Additionally, the juice and macerated leaves are utilized as a home cure for children's flatulence and diarrhea. They are converted into pills and suggested for infants suffering from colic and other gastrointestinal issues [8]. The tribal society used the herb as an astringent, anodyne, tonic, and alexipharmic agent. The leaves have been used in decoction or infusion with positive outcomes for scabies, fever, anemia, and a sluggish liver. The root's tincture is employed as a tonic, stimulant, and aperients. Various plant parts, either by themselves or in combination with other Indian plants, are used in many Indian and other Asian communities for neuralgia, fever recovery, and liver torpidity. The herb serves as the major constituent of a traditional home treatment that is employed as a febrifuge and bitter tonic [10].

Bioactive compounds of Andrographis

The aerial portions and roots of Andrographis paniculata contain a wide range of significant bioactive substances. Terpenoids, which make up a substantial amount of their constituents and medicinal capabilities, are the significant metabolites. The other components are flavonoids, polyphenols, xanthones, and macro-and trace elements.

Terpenoids

Diterpenoid lactones are the main terpenoid that are extracted from Andrographis paniculata's aerial parts and roots (table 2). The majority of the isolated and recognized diterpenoids from Andrographis paniculata, in terms of both quantity and occurrence, are andrographolide, deoxyandrographolide, and neoandrographolide [12]. Andrographolide is a white, crystalline substance with an extremely unpleasant taste. It has a variety of pharmacological characteristics and was initially extracted in pure form by Gorter in 1911. Andrographolide is an α-alkylidene γ-butyro-lactone molecule with three-OH groups at Carbon-3, 14, and 19 that is found primarily in leaves. Deoxyandrographolide and neoandrographolide are also dominant diterpenoids that are usually found in the aerial parts of plant. Several researchers have isolated these diterpenoids. Other diterpenes besides the prominent ones have also been discovered by several researchers, including a unique terpenoid (23-carbon) found in the plant's roots and aerial parts.

Flavonoids

Flavones are extracted from all parts of the herb (table 1). Flavones, such as 5, 7, 2, and 3'-tetra methoxy flavones, as well as 5-hydroxy-7, 2-, and 3-trimethoxyflavones, are found throughout the plant [22]. The root and aerial parts of the plant contain the flavone 7-O-methyl-dihydro wogonin, while the 1,2-methyl ether type of flavone is found in all portions of the plant. The flavonoids 5-hydroxy-7, 8, 2, and 5'-tetramethoxyflavone can be found throughout the entire plant. An instance of a flavone distributed throughout the entire plant is dihydroskullcapflavone [27, 28].

Table 1: Bioactive compounds of Andrographis paniculata

S. No. Compounds Basic structure type Extracted from plant parts Refer
1 Andrographolide Diterpenoid lactone

Aerial plants

parts

 [12]
2 Deoxyandrographolide [13, 14]
3. Neo-Andrographolide [13, 14]
4. Andrographolide D: (14-deoxy-11,12-didehydroAndrographolide) [15]
5 Andrographolactone [16]
6. Andrographanin Diterpene Leaves [31]
7. Andrographoside Diterpene Leaves [21]
8. 19-O-β-Dglucopyranosyl-entlabda-8(17) 13-diene-15,16,19-triol entlabdane Ent-labdane diterpenoids Aerial plants parts [17-20]
9. 3-O-β-Dglucopyranosyl-14,19-dideoxy andrographolide
10. 8-α-methoxy14-deoxy17β-hydroxy andrographolide entlabdane
11. 5,7,2’,3-tetramethoxy flavones. Flavonone All parts of a plant [23]
12. 5-hydroxy-7,2’,3’-trimethoxy flavones Flavone All parts of a plant [23]
13. 7-O-methyl-dihydro wogonin [24]
14. Flavone-1,2’methylethe [25, 26]
15. 5-hydroxy-7, 2', 3'-tri methoxyflavones Flavonoids All plant parts [27, 28]
16 Dihydroskullcapflavone Flavone All plant parts [27, 28]

Table 2: Other chemical constituents of Andrographis paniculata

S. No. Chemical constituents Extracted from a plant part Refer.
1. 1,8-dihydroxy-3,7-dimethoxy-xanthone Root of plant [29]
2. 4,8-dihydroxy-2,7-dimethoxy-xanthone
3. 1,2-dihydroxy-6,8-dimethoxy-xanthone
4. 3,7,8-trimethoxy-1-hydroxy-xanthone
5. Andrographidoid A-E [30]
6. Curvifloruside
7. Arabinogalactan Herbs [32]

Other compounds

In addition, using chromatography, four distinct xanthones found in the roots of Andrographis paniculata have been extracted and identified (table 2). They were identified as 1, 8-dihydroxy-3,7-dimethoxy-xanthone, 4,8-dihydroxy-2,7-dimethoxy-xanthone, 1,2-dihydroxy-6,8-dimethoxyxanthone and 3,7,8-trimethoxy-1-hydroxy-xanthone [29]. The roots of Andrographis paniculata were used to isolate five unusual noriridoids, including andrographolide A-E and curvifloruside. By Prajjal and his associates in 2007, arabinogalactan proteins were extracted from the dried herbs [32], and microelements (K and Ca) and trace elements (Cr, Mn, Co, Ni, Zn, Cu, Se, Rb, Sr, and Pb) were discovered and measured in the roots.

Pharmacological properties of Andrographis paniculata

Scientists have explored Andrographis paniculata's pharmacological qualities to confirm its usage as a therapeutic agent in the therapy of many illnesses as a result of its use in folk medicine, particularly in Asia [33, 34]. Studies have revealed that this plant have variety of biological activities, including antioxidant activity [35, 36], anti-bacterial [37, 38], anti-viral [39], cold and fever [40], anticancer activity [41, 42], urinary tract infection [43], and anti-diabetic activity [44, 45], cardiovascular activity [46, 47], immunomodulatory activity [48, 49] and anti-hepatotoxic [50, 51], etc

Antioxidant activity

In many European states and Asia, Andrographis paniculata is used as a natural antioxidant. A study of Verma et al., observed that how Kelmegh's aqueous extract affected the hepatic defense system in AKR mice having lymphoma [52]. He also observed that taking an oral dose of a plant's aqueous extract considerably increased the activity rate of glutathione-s-transferase, catalase, and superoxide dismutase. Andrographolide significantly affected the hepatic antioxidant defense system and lipid oxidation in control mice, according to Das et al., [53]. Its hepato-protective reactivity against hexa-chloro cyclohexane was also tested for oxidative injury. He discovered that plant extract and active ingredient andrographolide exhibits a antiradical activities against several pathophysiological oxidants using liver sub-cellular organelles of rat as model systems [54]. When the plant's antioxidant and anti-inflammatory properties were investigated, it was discovered that the methanolic extract inhibits the production of free radicals such as superoxide, hydroxyl radicals and nitric oxide in vitro system [55]. The RAW cells stimulated with lipo-polysaccharide (LPS), andrographolide decrease nitric oxide formation and stabilize the inducible synthase protein [56, 57]. Neoandrographolide, which was an extract from the EtOAc portion of methanol extract, inhibits in vitro and ex vivo NO production in Bacillus Calmette-Guéin (BCG)-induced peritoneal macrophages in mice [58].

Antioxidants are essential for the cure or mitigation of a variety of illnesses. Numerous clinical problems, including degenerative diseases, have been linked to the patho-physiology of natural antioxidants. It might accelerate the ageing process and progressive impairment of the immune function [59]. Additionally, it has been suggested that the phenolic content of drugs and their antioxidant activity may be related. The flavonoids are a group of phenolic compounds with bioactive qualities, including the capacity to scavenge free radicals, inhibit hydrolytic and oxidative enzymes, and serve as an anti-inflammatory [60].

A number of diseases in the human body are caused by free radicals. It may be important to consume natural oxidants as free radical scavengers in order to enhance the compromised immune system [88]. According to reports, the antioxidant constituents of plant materials buffer the body from damage produced by free radical-induced oxidative stress and protect against cancer and coronary heart disease [84]. Positive results were obtained from studies on Andrographis paniculata's antioxidant activities in conjunction with the herb's diterpenoid components. There are; however, very few studies comparing the antioxidant properties of Andrographis paniculata to those of synthetic antioxidants.

Anti-microbial activity

Andrographis paniculata has been extensively used against the activity of various bacteria, viruses, and parasites. It was observed that ethanolic leaf extract decreased the growth of E. coli and S. aureus in vitro. In vitro development of Proteus vulgaris to be inhibited by a 50% methanol extract of Andrographis paniculata. Another study revealed that significant anti-microbial activity was found with the aqueous extract of andrographolide and arabinogalactan proteins of Andrographis paniculata [32]. Streptococcus mutant and S. mutans adhesion are inhibited by plant ethanol extract at the necessary doses in vitro (0.5 percent). A study found that Andrographis water extract may have potential antibacterial effects on both strains of bacteria. According to Wiart et al., Andrographis paniculata Nees' ent-labdane diterpenes reduced the propagation of the herpes virus and had no discernible lethal effects at viricidal concentrations [39, 61]. At 0.05 mg/ml concentration, the chloroform extract greatly slowed the growth of the malaria parasite within 24 h of incubation [62]. Asian societies have long relied on the leaves of Andrographis paniculata to reduce body temperatures and relieve fever. According to Misra et al., a methanolic extract of kalmegh has antimalarial action against the malaria-causing organism Plasmodium berghei [63]. Studies of Andrographis conducted in vitro and vivo showed that it has anti-malarial capabilities that can be investigated further to produce potent anti-malarial drug in future [86].

Hepato-protective activity

In Indian medical systems, Andrographis paniculata is commonly utilised as a hepatostimulant and hepatoprotective. The hepatoprotective activity of Andrographis paniculata was reported by many groups of researchers. There is few research on the impact of Andrographis paniculata crude extracts on liver function. Andrographolide significantly increased choleretic effects on anaesthetized guinea pigs, according to Shukla et al. [64]. Andrographolide, a typical hepatoprotective drug, was found to be more effective (0.75–12 mg/kg) in a comparative analysis than silymarin [65]. According to reports, Andrographolide increases bile flow significantly in animals, making digestion easier. After a study of consumption of Andrographolides accumulation in different organs like the brain, spleen, heart, lung, kidney, liver, intestine, etc. Researchers discovered that both assimilation and removal were quick; 90% of the substance was eliminated through the renal and gastrointestinal tract within 48 h. They discovered that a plant might effectively heal hepatitis [66].

Anti-fertility

The use of Andrographis paniculata as natural medicine is increasing day by day; hence its adverse effects on the human body if any also is the topic of interest. In regard to this, Andrographis paniculata's potential impact on male and female reproduction has been studied. A study by Akbarsha et al., reported that Andrographis paniculata's antispermatogenic and antiandrogenic effects were demonstrated in male albino rats fed 20 mg/day dose of 60 d in leaf powder form, it resulted in the loss of spermatogenesis, degeneration, alternations in the seminiferous tubules, sperm vesicle, ventral prostate gland, coagulating gland and regression of the Leydig cells [67]. According to research by Zoha et al., female mice did not pregnant after taking 2 gm/kg weight per day for six weeks plant powder whereas 95.2% of female control mice did not receive Andrographis paniculata became pregnant. This suggests that the herb has a strong anti-fertility effect and should not be used while pregnant [68]. Similar effects were also seen in male Wistar albino rats after 48 d of oral administration of andrographolide. The dried extract of Andrographis paniculata, according to Burgos et al., blocks voltage-sensitive calcium channels to cause uterine relaxation [43].

Anti-malarial activity, cold, and fever

For many years, Asian societies have utilized the leaves of Andrographis paniculata to treat fever and reduce body temperatures. According to Misra et al., Kalmegh’s methanolic extract exhibits anti-malarial efficacy against Plasmodium berghei, malaria-transmitting parasites [63]. The extract clearly demonstrates suppression of the parasite's ability to reproduce. It has also been found that the lactate dehydrogenase (LDH) assay can inhibit anti-malarial efficacy against Plasmodium falciparum [85]. Compounds 1, 2-dihydroxy-6, 8-dimethoxyxanthone, which has an IC50 value of 4 μg/ml, were found to have significant anti-plasmodial action against Plasmodium falciparum in vitro experiments. The most active xanthones were those with hydroxyl groups in the second position, while those with the hydroxyl group in the first, fourth, or eighth positions had very little activity [29].

Additionally, a pilot double-blind study on the use of the herbal treatment ‘Kang Jang’ to prevent the common cold was reported (standardized to 4 percent Andrographolides). It was discovered that "Kang Jang" (doses of 200 mg daily) showed a 30% reduction in the incidence of cold [69]. The usage of Andrographis paniculata in the treatment and prevention of influenza and cold flu viruses has been recognized [70]. In a separate study, 152 adult patients with pharyngotonsillitis were examined, and after seven days, the patients were randomly assigned to receive either paracetamol or a 3 or 6 g daily dose of the herb [86, 87]. On day third, paracetamol or high-dose Andrographolide was significantly more effective than low-dose Andrographolide in reducing fever and sore throat. On day seven, the same clinical improvement was found [71].

Anti-HIV activity

When the anti-HIV properties of Andrographis paniculata were examined, it was discovered that andrographolide changes cellular signal transduction mechanisms to inhibit the spread of the virus and halt disease progression. The anti-HIV and cytotoxic effects of bis-andrographolide ether, andrographolide, 14-deoxy-11,12-didehydroandrographolide, andrograpanin, as well as 5-hydroxy-7,8-dimethoxyflavanone and 5-hydroxy-7,8-dimethoxyflavone, were investigated [72]. Clinical experiments conducted by Calabrese et al. showed anti-HIV effectiveness, Dehydro andrographolide succinic acid monoester (DASM) inhibits HIV in vitro. A doses between 1.6 and 3.1 mcg/ml, was not harmful to the H9 cell. Additionally, dehydroandrographolide succinic acid monoester inhibited two additional HIV-1 strains and one other HIV-2 strain [73]. For three weeks, 5, 10, and 20 mg/kg doses of andrographolide were given, and the lymphocyte level of HIV individuals significantly increased [74, 75].

Anti-venom activity

According to conventional medical practice, Andrographis paniculata is a natural remedy for snake bites. Mice poisoned with cobra venom were given an intraperitoneal injection of ethanolic extract from leaves (25 g/kg body weight), which significantly delayed respiratory failure and death. At 2 mg/ml, this extract also caused contractions in the guinea-pig ileum. These contractions were unaffected by antihistamines but were boosted by physostigmine and prevented by atropine. According to the study, the extracts' anti-venom properties may be explained by a large increase in muscarinic activity rather than by altering the activation of nicotinic receptors. In mice, Andrographis paniculata ethanolic extract showed some protective effects against red scorpion venom [76].

Anticancer activity

In numerous prostate cancer cell lines, andrographolide acts as a therapeutic agent. Andrographolide is quickly digested when used orally, unlike other cytotoxic anticancer medications. A 2-cell line panel made up of the colon (HCT-116) and breast (MCF-7) cancer cell lines showed antitumor activity as well [47]. In a study conducted by Singh using various cancer cell lines, they found that it has the potential to be chemoprotective against chemotoxicity, including carcinogenicity. In late-stage malignancies, where there is an increase in the cytotoxic activity of natural killer cells (NK) and tumor necrosis factor-alpha (TNF-alpha), they utilize this combination. Diterpenes, flavonoids, and stigmasterols are all present in the plant extract of Andrographis paniculata, with Andrographolide being the main active diterpenoid and having potent cytotoxic activity against human epidermoid cancer and the P388 mouse leukemic cell line [77, 86].

Antidiabetic activity

Oxidative stress and diabetes are closely connected diseases. As free radicals, oxygen plays a significant role in diabetes complications. According to a study on blood glucose, when an Ayurvedic formulation supplemented with this plant, i.e., IIogen-Excel, is taken orally for 60 d, total hemoglobin, hepatic glycogen, and plasma insulin levels all increase while blood glucose levels are markedly reduced [78]. Researchers studied how the plant influenced the estrous cyclicity of rats that had been given alloxan to make them diabetic, and they found that Kalmegh has the ability to reverse the rats' abnormal estrous cycles. It was also reported that water extract (1 g/kg body weight) had a significant (P 0.001) hypoglycemic effect on experimental rabbits [79]. In a dose-dependent way, andrographolide oral therapy reduced the levels of plasma glucose in streptozotocin-induced diabetic rats

Cardiovascular activity

Numerous researchers have published independent reports on the cardiovascular activity of A. paniculata and its chemical components. Experimental animal’s artery wall thickening was successfully prevented by the herb's extracts. The plant extract also has the additional benefit of triggering fibrinolysis, a bodily process that naturally breaks up clots. The smooth muscle in blood vessel walls was relaxed by a plant extract; it stopped blood vessels from narrowing and restricting blood flow to all body organs. According to separate findings by Zhang et al., the growth of aortic smooth muscle cells is inhibited by andrographolide in vitro. Andrographolide may be used in patients with a variety of cardiac diseases. The aqueous fractions of water: n-butanol extract significantly lowers MAP without significantly lowering heart rate, whereas the ethyl acetate fraction and andrographolide have no effect on mean arterial blood pressure (MAP). According to reports, it boosted the uptake of labeled glucose in cultured myoblast cells, which may have an effect on lowering blood glucose levels. Researchers discovered a hypotensive effect of its aqueous extract in rats during a clinical trial, and they postulated that the aqueous extract of Andrographis paniculata may lower spontaneously hypertensive rats' systolic blood pressure by reducing plasma levels of angiotensin-converting enzyme and free radicals as well [80, 81].

Immunomodulatory activity

According to reports, andrographolide has immunostimulant and suppressive properties. A diterpene lactone called andrographolide has been found to have immunomodulatory properties that are linked to increased human peripheral blood lymphocyte proliferation, key cytokine production, and the total blood cells have increased immunological activation marker expression (like INF-, neopterin, and 2-microglobulin). HPBLs (human peripheral blood lymphocytes) were activated by the immune stimulatory action of andrographolide described in vitro PHA through increased cell proliferation and IL-2 production. Additionally, it has been noted that andrographolide prevented macrophages activated by lipopolysaccharide from producing TNF and IL-12. According to reports, the plant is a powerful immune system booster, and andrographolide can effectively suppress T-cell stimulation both in vitro and vivo, a property that may be valuable for preventing harmful T-cell reactions [82, 83].

CONCLUSION

Andrographis paniculata has traditionally been employed to treat a variety of ailments. Several numerous formulations, extracts, and pure compounds of Andrographis paniculata are used against various bioactivities, such as antioxidant, anti-inflammatory, anti-microbial, anti-malarial, anti-cold and fever, anti-viral, hepatoprotective, anti-fertility, anti-venom, anti-cancer, anti-diabetic, cardiovascular activity, and immunomodulatory activity. The major chemical constituents are diterpenoids, flavonoids, and polyphenols present on the aerial part of the plant. Andrographolide is one of the most prevalent and prolific diterpenoids. It treats and prevents a number of human ailments. Andrographis paniculata has seen a significant surge in demand in recent years due to its incredible medicinal potential. Numerous clinical trials were conducted without any negative outcomes, proving the plant's safety and significance for people. Cultivation can be an excellent alternative to satisfy business demand. To learn more about novel bioactive compounds and improve the bioactivity of the original chemicals, more research is still required.

ACKNOWLEDGMENT

I appreciate my institution's head giving me all the assistance I needed to complete this review. I also want to express my gratitude to my friends, who have been great support and inspiration to me throughout the investigation.

AUTHORS CONTRIBUTIONS

All the authors have contributed equally.

FUNDING

Nil

CONFLICT OF INTERESTS

Declared none

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