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Antiviral and Immunostimulant Activities of Andrographis paniculata

DOI:10.4308/hjb.22.2.67
Authors:
Churiyah Churiyah at Badan Pengkajian dan Penerapan Teknologi
Churiyah Churiyah
Olivia Bunga Pongtuluran
Olivia Bunga Pongtuluran
Olivia Bunga Pongtuluran
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Elrade Rofaani at Ecole Normale Supérieure de Paris
Elrade Rofaani
Tarwadi Tarwadi at BRIN-National Agency for Research and Innovation
Tarwadi Tarwadi
  • BRIN-National Agency for Research and Innovation
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Abstract and Figures

Andrographis paniculata (Burm. f.) Nees is a medicinal plant which was reported to have anti HIV, anti pathogenic bacteria and immunoregulatory activities. The research purpose was to investigate the activity of Andrographis paniculata ethanol extract as antiviral and immunostimulant. A. paniculata leaves oven-dried, then grinded and macerated with ethanol 90%, and the extract then analyzed using High Performance Liquid Chromatography (HPLC) to determine the content of active compounds andrographolide. The antiviral activity of the extract was determined by observing its ability on inhibiting virus load in A549 cells transfected with Simian Retro Virus (SRV) by Real Time – Polymerase Chain Reaction (RT-PCR) analysis. The immunostimulant activity of extract was determined by its ability to induce lymphocytes cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Our result indicated that the A. paniculata ethanol extract inhibited the SRV virus titer similar to the positive control Lamivudine, and it was not toxic to the A459 cell line. Furthermore, low concentration (1 μg/mL) of A. paniculata extract could stimulated lymphocyte cell proliferation about 38% compared to the control lymphocyte cell without any treatment.
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... The proteins, chlorophyll, regular sugars are the primary constituents of phytochemicals and alkaloids, terpenoids, phyto sterols, flavonoids, glycosides, tannins and phenolic compounds are the secondary constituents (Li et al., 2007) [14] . Major phytochemicals of A. paniculata are diterpenoids, flavonoids and polyphenols (Churiyah et al., 2014) [5] . Andrographolide (AD) is the major compound in terms of bioactive properties and abundance which is present in A. paniculata. ...
... Andrographolide is the most predominant diterpenoids and it is bitter in taste and brown in colour (Siripong et al., 1992) [24] . The presence of alkaloids is very crucial as it has many pharmacological importance, as it can act as antiprotozoal, has cytotoxic activity, antidiabetic properties (Zhang and Tan, 2000) [26] , as antimalarial, analgesic, immunostimulant as well as anti-inflammatory properties (Appiah et al., 2017;Churiyah et al., 2015) [1,5] . Flavonoids present in the extract are known to inhibit tumorous growth and provide protection against various gastrointestinal infections. ...
... Andrographolide is the most predominant diterpenoids and it is bitter in taste and brown in colour (Siripong et al., 1992) [24] . The presence of alkaloids is very crucial as it has many pharmacological importance, as it can act as antiprotozoal, has cytotoxic activity, antidiabetic properties (Zhang and Tan, 2000) [26] , as antimalarial, analgesic, immunostimulant as well as anti-inflammatory properties (Appiah et al., 2017;Churiyah et al., 2015) [1,5] . Flavonoids present in the extract are known to inhibit tumorous growth and provide protection against various gastrointestinal infections. ...
Determination of phytochemicals present in ethanolic extracts of Andrographis paniculata
Article
Full-text available
  • Sep 2023
The study was conducted to analyse the phytochemical constituent of Andrographis paniculata. A 60% ethanolic extract was prepared and the different phytochemicals were qualitatively analysed by standard protocol. A total of ten numbers of phytochemicals were tested, out of which the extract was positive for alkaloid, phenolic compunds, steroids, terpenoids, saponins, tannins, flavonoids and negative for glycosides, amino acids and proteins. Analysis was done on the basis of colour change and precipitate formation. Presence of different important phytochemicals indicates the importance of the plant as herbal medicine.
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... It appeared from the study a major rise in the mean CD4(+) lymphocyte level of HIV even though with no considerable changes in mean plasma HIV-1 RNA levels throughout the trial. These findings demonstrated that due to andrographolide which causes a rise in CD4 (+) lymphocyte levels may be the reason of inhibition of HIV-induced cell cycle dysregulation in HIV-1 infected individuals [37] . The outcome of recent study summarized that the derivatives of andrographolide may have the capability towards preventing HIV infection [38] . ...
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... The major active compound contained in the leaves of A. paniculata is Andrographolide (Jayakumar et al., 2013;Churiyah et al., 2015). Andrographolide is a labdane diterpenoid that is used in 26 Ayurvedic formulations for the treatment of liver disease (Pandey and Rao, 2018). ...
Development of analysis method of andrographolide from Andrographis paniculata using UPLC-PDA
Article
  • Feb 2023
Andrographis paniculata is an herbaceous plant belonging to the family Acanthaceae dan also known as the “King of Bitters”. It has been utilized as traditional medicines by the local people in India and Southeast Asia. Many studies have been reported regarding the pharmacological activities of A. paniculata and Andrographolide. Currently, in addition to compound isolation and bioactivity assays, validation of analysis method is also required. Validation is used to demonstrate that the method used is appropriate and the results are precise and accurate. The method used needs to be simple, concise, precise, accurate, and widely used. The analysis in this study was carried out using Ultra-Performance Liquid Chromatography because the instrument operates at high pressure. In addition, the system uses fine particles which can reduce column length as well as solvent and time consumption. This study aims to validate analytical methods in determining the contents of andrographolide in an A. paniculata Leaves. The analytical method was validated through a Waters Alliance UPLC System with photodiode array (PDA) detector. The A. paniculata extract and standard solutions of Andrographolide were analyzed using reverse-phase C18 column which was maintained at 40°C. A mobile phase of 0.1% formic acid in acetnotirile and 0.1% formic acid in water was used at flow rate of 0.3 mL/min to achieve gradient elution. The linearity of the andrographolide showed excellent results (R2= 0.9999) in the concentration range of 7.8–250.0 µg/mL. The LOD and LOQ values of andrographolide were 0.068 µg/mL and 0.205 µg/mL, respectively. The intra-day and inter-day relative standard deviation (RSD) and relative error (RE) accuracy values of andrographolide were <±15. The quantitative analysis found that A. paniculata extract contained 12.45 ±0.06 mg/g of Andrographolide. This developed UPLC-PDA method was proven to be precise, specific, sensitive, and accurate for routine quality assessment of raw material of Andrographis paniculata leaves content.
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... The entire plant and Andrographolide have shown various pharmacological activities such as stable pumping heart and good circulation of blood (4), agent for the treatment of fever, cold, laryngitis, diarrhea, inflammatory diseases, respiratory infections, and a variety of other chronic and infectious diseases (5). anti-inflammatory (6), antipyretic (7), immunostimulant (8), antiviral (9), anti-bacterial (10), hepatoprotective (11), anti-fertility (12), anti-thrombotic (13), anti-diabetic (14), anti-cancer (15), and anti-oxidant (16). Study reported that Andrographis paniculata is a immunoprotective ayurvedic herb against respiratory viral infections (17). ...
Quantification and Standardization of Andrographolide in Andrographis Paniculata Samples by Validated RP-HPLC and HPTLC Methods
Article
Andrographis paniculata (family Acanthaceae) is known as Kalmegh, one of the traditionally used important medicinal plant contains several biologically active phytochemical including andrographolide. A. paniculata is broadly used by healthcare practitioners in India and also used in different traditional medicinal system. In this study, the leaves of A. paniculata were collected from West Medinipur, East Medinipur, South 24 Parganas, Purulia and Hooghly district of West Bengal, India. This study aiming towards validation and development of a simple, precise and reproducible reverse-phase high-performance liquid chromatography (RP-HPLC) and high-performance thin layer chromatography (HPTLC) methods for quantification of andrographolide in A. paniculata extracts. The validated RP-HPLC and HPTLC study confirmed that different concentrations of andrographolide content present in the plant samples, which are collected from above different districts of West Bengal, India. The amounts of andrographolide were found to be 2.71% (w/w), 3.19% (w/w), 1.83% (w/w), 1.73% (w/w) and 2.94% (w/w) in RP-HPLC study and 2.13% (w/w), 2.51% (w/w), 1.01% (w/w), 1.25% (w/w) and 2.15% (w/w) in HPTLC study. This precise, reproducible, accurate and specific method can be used for the quantification of andrographolide in kalmegh, as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines recommendations.
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Antioxidant Effects of Catechins (EGCG), Andrographolide, and Curcuminoids Compounds for Skin Protection, Cosmetics, and Dermatological Uses: An Update
Article
Full-text available
  • Jun 2023
Here we have chosen to highlight the main natural molecules extracted from Camellia sinensis, Andrographis paniculata, and Curcuma longa that may possess antioxidant activities of interest for skin protection. The molecules involved in the antioxidant process are, respectively, catechins derivatives, in particular, EGCG, andrographolide, and its derivatives, as well as various curcuminoids. These plants are generally used as beverages for Camellia sinensis (tea tree), as dietary supplements, or as spices. The molecules they contain are known for their diverse therapeutic activities, including anti-inflammatory, antimicrobial, anti-cancer, antidiabetic, and dermatological treatment. Their common antioxidant activities and therapeutic applications are widely documented, but their use in cosmetics is more recent. We will see that the use of pharmacomodulated derivatives, the addition of co-antioxidants, and the use of various formulations enable better skin penetration and greater ingredient stability. In this review, we will endeavor to compile the cosmetic uses of these natural molecules of interest and the various structural modulations reported with the aim of improving their bioavailability as well as establishing their different mechanisms of action.
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Evaluations of Andrographolide-Rich Fractions of Andrographis paniculata with Enhanced Potential Antioxidant, Anticancer, Antihypertensive, and Anti-Inflammatory Activities
Article
Full-text available
  • Mar 2023
Andrographis paniculata is widely used as a traditional medicine in Asian countries. It has been classified as a safe and non-toxic medicine by traditional Chinese medicine. The investigation of the biological activities of A. paniculata is still focused on the crude extract and isolation of its main active compound, andrographolide, and its derivatives. However, the use of andrographolide alone has been shown to exacerbate unwanted effects. This highlights the importance of developing a fraction of A. paniculata with enhanced efficacy as an herbal-based medicine. In this study, the extraction and fractionation of A. paniculata, followed by quantitative analysis using high-performance liquid chromatography coupled with a DAD detector, were established to quantify the andrographolide and its derivative in each fraction. Biological activities, such as antioxidant, anticancer, antihypertensive, and anti-inflammatory activities, were evaluated to study their correlations with the quantification of active substances of A. paniculata extract and its fractions. The 50% methanolic fraction of A. paniculata exhibited the best cytotoxic activities against CACO-2 cells, as well as the best anti-inflammatory and antihypertensive activities compared to other extracts. The 50% methanolic fraction also displayed the highest quantification of its main active compound, andrographolide, and its derivatives, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and andrograpanin, among others.
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Traditional medicine herbs as natural product matrices in cancer chemoprevention: A trans pharmacological perspective (scoping review)
Article
  • Feb 2023
Emerging evidence on molecular biology related to tumors, inflammation, and immunity, highlights their architectural commonality shifting cancer treatment paradigms toward more economical prevention than treatment. Statistical surveys reveal exponentially growing herbal drug supplementation in cancer worldwide as vast pre‐clinical and clinical data unravel their multi‐mechanistic pharmacology. The integrative oncological approach calls for more “holistic” principles to be amalgamated into cancer care. New cancer drug development from herbs need not be limited by the archetypal ‘RCT‐Standardization’ bottlenecks. Based on comprehensive literature scoping as per Prisma‐ScR guidelines, we herein concurrently reviewed evidence‐based research reports of selected Indian Traditional Medicine (ITM) herbs of anticancer repute in parallel with their holistic therapeutics; a rationalistic exploration of ITM's scientific genre. Their synergy effect on cancer revisited using a trans‐pharmacological approach validates ITM's seemingly simplistic health/disease equation model, showing a fresh new avenue for re‐purposing whole herbal drug complexes in cancer management. Herbal drugs as per ITM are natural matrices whose dynamics of interaction in the etiopathology of cancer are conceptually and mechanistically integrative. Lateral perspective to the same as laid out in this review holds the key to their effectual development as more tangible cancer chemopreventives/new drug targets/leads if not as new pharmacological tools. Emerging cancer research drives a holistic perspective to cancer care. Integrative oncology changes treatment paradigms toward more economical prevention. Molecular action mechanism of Ayurvedic herbs points toward their matrix effect. Current research enables trans pharmacological view to holistic therapeutics. Such lateral perspective poised to supplement tedious high premium research.
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The Role of Andrographis paniculata in Modulating the Immune Response in Cancer-Associated Chronic Inflammation, Angiogenesis, and Metastasis
Article
Full-text available
  • Jun 2022
The immune system plays an essential role in cancer pathogenesis through providing an inflammatory immune response. Chronic inflammation causes tumor growth, angiogenesis, and metastasis facilitated by interactions between tumor, immune, and stromal cells in the tumor microenvironment (TME). Various inflammatory mediators and growth factors secreted by cells in the TME exert a synergistic effect on cancer promotion. Thus, the development of cancer therapies that lead to inhibition of the activity of immune cells, cytokines, chemokines, and cancer-inducing growth factors is a promising therapeutic strategy. Andrographis paniculata (A. paniculata) is an ethnomedicinal plant with immunomodulatory and anticancer activity. A. paniculata can also inhibit the resistance of chemotherapy agents associated with the TME as adjuvant chemotherapy. This review focuses on the mechanism of A. paniculata in suppressing cancer-associated chronic inflammation, angiogenesis, and metastasis through modulation of the immune response. The results show that A. paniculata exerts anticancer effects directly targeting cancer cells, inhibiting cancer growth by modulating immune responses. A. paniculata exerts anticancer effects by inhibiting the production of cytokines, growth factors, and chemokines via the nuclear factor-kappa B (NF-ĸB), mitogen-activated protein kinase (MAPK), Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways. In addition, this review provides a new hypothesis regarding the potential of A. paniculata to serve as an anticancer agent that can inhibit cancer cell proliferation at the angiogenesis and metastatic stages through regulating inflammation due to interactions between cancer cells, immune cells, and stromal cells in the TME.
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Zingiber officinale, Piper retrofractum and Combination Induced Apoptosis and p53 Expression in Myeloma and WiDr Cell Lines
Article
Full-text available
  • Sep 2012
In previous studies, Zingiber officinale, Piper retrofractum, and the combination showed cytotoxic activity, induced apoptosis, and p53 expression of HeLa, T47D, and MCF-7 cell lines. This study was conducted to investigate the cytotoxic and apoptotic activity of Zingiber officinale (ZO), Piper retrofractum (PR), and the combination as well as their effect to p53 expression on Myeloma and WiDr cells. The powder of ZO, PR, and ZO + PR combination (1:1) were macerated with 96% ethanol for 3 x 24 hours. MTT cytotoxic assay was performed on Myeloma and WiDr cell lines. Apoptotic cells were stained with ethidium bromide and acridine orange. Imunohistochemical expression of p53 was examined on Myeloma and WiDr cell lines. Doxorubicin was used as positive control in all assays. Results showed that ZO, PR, and ZO + PR combination had cytotoxic activity on Myeloma cells with IC50 of 28, 36, and 55 mg/ml respectively and WiDr cell lines with IC50 of 74, 158, and 64 mg/ml respectively, induced apoptotic activity, and increased p53 expression on Myeloma and WiDr cells. These results suggest that ZO, PR, and their combination induced Myeloma and WiDr cells in apoptosis through p53 expression.
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Immunosuppresive Effect of Medicinal Plants of Kolli Hills on Mitogen-Stimulated Proliferation of The Human Peripheral Blood Mononuclear Cells in Vitro
Article
Full-text available
Four medicinal plant species were collected from the Kolli hills of Tamil Nadu and were screened for their immunosuppressive effect. The plants were shade dried and extracted with methanol. The crude methanol extracts were tested for inhibition of lymphocyte proliferation via lymphocyte proliferation assay by 3thymidine uptake. The test plants were Justicia gendarussa, Plumbago indica, Aloe vera, and Aegle marmelos. Among the plants tested J. gendarussa (100 µg/ml) showed the highest lymphocyte inhibition (84%). Sequential extraction of J. gendarussa in various solvents (n-hexane, benzene, ethyl acetate, chloroform, acetone, ethanol, and water) confirmed that all of the above extracts at 50 µg/ml, aqueous extract inhibited lymphocyte proliferation. Further, 17 high performance liquid chromatography fractions were collected for the aqueous extract and fraction no. 15 showed maximum inhibition of lymphocyte proliferation. The present study indicates that these extracts should be investigated further for the possible presence of immunosuppressive components.
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A phase I trial of Andrographolide in HIV positive patients and normal volunteers
Article
Full-text available
A phase I dose-escalating clinical trial of andrographolide from Andrographis paniculata was conducted in 13 HIV positive patients and five HIV uninfected, healthy volunteers. The objectives were primarily to assess safety and tolerability and secondarily to assess effects on plasma virion HIV-1 RNA levels and CD4+ lymphocyte levels. No subjects used antiretroviral medications during the trial. Those with liver or renal abnormalities were excluded. The planned 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/mm3 to 501 cells/mm3; p = 0.002). There were no statistically significant changes in mean plasma HIV-1 RNA levels throughout the trial. Andrographolide may inhibit HIV-induced cell cycle dysregulation, leading to a rise in CD4+ lymphocyte levels in HIV-1 infected individuals. Copyright © 2000 John Wiley & Sons, Ltd.
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A review on immunostimulatory plants
Article
Full-text available
  • Feb 2011
The use of medicinal plants to cure human illness has been practiced from time immemorial. Nowadays, the vast majority of people still rely on their traditional materia medica for their daily health care needs. The use of plant species for treatment of various human ailments has been mentioned in Ayurveda and other Indian literature. Some of these drugs are believed to enhance the natural resistance of body to infection. So there are many plants having immunostimulatory activity. This paper reviews plants which have shown reported immunostimulatory activity.
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ChemInform Abstract: Anti-HIV Activity of Semisynthetic Derivatives of Andrographolide and Computational Study of HIV-1 gp120 Protein Binding.
Article
  • Jul 2012
Andrographolide, a diterpene lactone of the Andrographis paniculata, displays anti-HIV activity in vitro. A series of andrographolide derivatives have been synthesized and evaluated for their anti-HIV activity in a cell-free virus infectivity assay using TZM-bl cells. As compared to andrographolide, 3-nitrobenzylidene derivative 6 showed higher in vitro anti-HIV activity, whereas 2',6'-dichloro-nicotinoyl ester derivative 9 showed higher Therapeutic Index. The andrographolide and its derivatives, 6 and 9, inhibited gp120-mediated cell fusion of HL2/3 cells (expressing gp120 on its surface) with TZM-bl cells (expressing CD4 and co-receptors CCR5 & CXCR4). Further, computational studies revealed that these molecules bind to the important residues of V3 loop of gp120. These results suggest that andrographolide derivatives may be promising candidates for prevention of HIV infection.
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Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats
Article
A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats.
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A review on immunostimulatory plants
Article
  • Feb 2011
Abstract: The use of medicinal plants to cure human illness has been practiced from time immemorial. Nowadays, the vast majority of people still rely on their traditional materia medica for their daily health care needs. The use of plant species for treatment of various human ailments has been mentioned in Ayurveda and other Indian literature. Some of these drugs are believed to enhance the natural resistance of body to infection. So there are many plants having immunostimulatory activity. This paper reviews plants which have shown reported immunostimulatory activity.
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