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A3
Anti-viral Anti-tumoural Anti-malignancy. Viral and bacterial infections. Antimicrobial


INGREDIENTS % Daily Value
Andrographolide 95%
Taraxasterol 20%(5:1)
Chlorogenic acid 25%





† Daily Value not established.




RESEARCH

Andrographolide
Andrographolide is an anti-pyretic, anti-inflammatory and immune enhancing compound. Its anti-inflammatory properties are due to the stimulation of adrenocortical hormone release and ACTH secretion.
Andrographolide

Evaluation of Immunomodulatory Activity of an Extract of Andrographolides from Andographis paniculata.
Naik SR, Hule A.
The immunomodulatory activity of HN-02, an extract containing a mixture of andrographolides (i.e., andrographolide [88 +/- 5 %] plus 14-deoxyandrographolide and 14-deoxy-11,12 didehydroandrographolide together [12 +/- 3 %]) in a pure powder form was evaluated at 1.0, 1.5, and 2.5 mg/kg on different IN VIVO and IN VITRO experimental models. In a delayed-type hypersensitivity (DTH) mouse model, potentiation of the DTH reaction was observed after treatment with cyclophosphamide (CYP) and HN-02 individually. However, CYP potentiation of the DTH reaction was reversed by HN-02 pretreatment.
Furthermore, HN-02 treatment elevated the depressed hemagglutination antibody (HA) titer and increased the number of plaque-forming cells (PFCs) in the spleen cells of mice that had been treated with CYP and challenged with sheep red blood cells (SRBC). Further, it was also found that HN-02 treatment stimulated phagocytosis in mice. A significant increase in total WBC count and relative weight of spleen and thymus was observed in mice during 30 days of treatment with HN-02. The present experimental findings demonstrate that HN-02 has the ability to enhance immune function, possibly through modulation of immune responses altered during antigen interaction, and to reverse the immunosuppression induced by CYP. Planta Med. 2009 Mar 4.

Immunostimulant agents from Andrographis paniculata.
Puri A, Saxena R, Saxena RP, Saxena KC, Srivastava V, Tandon JS.
EtOH extract and purified diterpene andrographolides of Andrographis paniculata (Acanthaceae) induced significant stimulation of antibody and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) in mice. The plant preparations also stimulated non-specific immune response of the animals measured in terms of macrophage migration index (MMI) phagocytosis of 14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and non-specific immune response was, however, of lower order with andrographolide than with the EtOH extract, suggesting thereby that substance(s) other than andrographolide present in the extract may also be contributing towards immunostimulation. J Nat Prod. 1993 Jul;56(7):995-9

Synthesis and evaluation of antibacterial activities of andrographolide analogues.
Jiang X, Yu P, Jiang J, Zhang Z, Wang Z, Yang Z, Tian Z, Wright SC, Larrick JW, Wang Y.
Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used for many years to treat a variety of diseases including bacterial and viral infections. Andro was recently reported to act by inhibiting the bacterial quorum sensing system. We have synthesized several Andro analogues and investigated their antibacterial activity and mechanism of action.
The new compounds were found to be much more potent than the parent Andro in inhibiting bacterial growth and quorum sensing system. Compounds 5 and 7 significantly reduced virulence factor production. Compound 7 completely inhibited Pseudomonas aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic activity with conventional antibiotics. These findings suggest that compound 7 may be the basis for future drug development to combat the unmet needs of virulence factor production, biofilm formation and antibiotic resistance. Eur J Med Chem. 2009 Jul;44(7):2936-43. Epub 2008

In vitro and in vivo anti-inflammatory effects of andrographolide.
Abu-Ghefreh AA, Canatan H, Ezeamuzie CI.
Andrographolide - the major active principle isolated from the plant Andrographis paniculata, has been shown to possess a strong anti-inflammatory activity. The possibility that the drug may affect asthmatic inflammation, through inhibition of the relevant inflammatory cytokines, has not been explored. The purpose of this study was, firstly, to investigate the ability of andrographolide to inhibit the release of inflammatory cytokines in vitro in a model of non-specific inflammation and subsequently to determine whether such effect can also be exerted in vivo in allergic lung inflammation.
LPS-induced TNF-alpha and GM-CSF release from mouse peritoneal macrophages was inhibited by andrographolide in a concentration-dependent manner. The concentration of the drug producing 50% inhibition was 0.6 microM for TNF-alpha and 3.3 microM for GM-CSF. The maximal inhibition achieved (at 50 microM) was 77% and 94%, respectively, for the two cytokines. The drug was as efficacious as dexamethasone, but about 8-12 times less potent. The drug also suppressed LPS-induced expression of mRNA for the two cytokines, suggesting that this effect may contribute to the mechanism underlying its anti-inflammatory effects. In the in vivo study, intra-peritoneal treatment of ovalbumin-immunized and nasally-challenged mice with andrographolide significantly inhibited the elevation of bronchoalveolar fluid (BAF) levels of TNF-alpha and GM-CSF in a dose-dependent manner, with 30 mg/kg producing an inhibition of 92% and 65% of the cytokines, respectively) and almost completely abolishing the accumulation of lymphocytes and eosinophils. These results provide evidence that andrographolide is an effective anti-inflammatory drug that is active in vitro and in vivo, and affects both non-specific as well as antigen/antibody-dependent lung inflammation. Thus, andrographolide has the potential to be used in a variety of inflammatory conditions, including allergic lung inflammation. Int Immunopharmacol. 2009 Mar;9(3):313-8.

A randomized, controlled study Andrographolide versus amantadine in the treatment of influenza in Volgograd.
Kulichenko LL, Kireyeva LV, Malyshkina EN, Wikman G.
Volgograd Outpatient Clinic, Department of Outpatient Therapy.
Two randomized, parallel-group clinical studies with a verum and a control group were performed to investigate the effect of a standardized extract of Andrographis paniculata in the treatment of diagnosed influenza viral infection. The pilot study was performed on 540 patients with 71 Andrographolide treated patients with the second phase conducted enrolling 66 patients. The differences in the duration of sick leave and frequency of post-influenza complications indicate that Andrographolide not only contributes to quicker recovery, but also reduces the risk of post-influenza complications.

Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata.
Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R.
Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad, India-500050. sriramrajagopal@drreddys.com
Andrographis paniculata plant extract is known to possess a variety of pharmacological activities. Andrographolide, the major constituent of the extract is implicated towards its pharmacological activity. We studied the cellular processes and targets modulated by andrographolide treatment in human cancer and immune cells. Andrographolide treatment inhibited the in vitro proliferation of different tumor cell lines, representing various types of cancers. The compound exerts direct anticancer activity on cancer cells by cell-cycle arrest at G0/G1 phase through induction of cell-cycle inhibitory protein p27 and decreased expression of cyclin-dependent kinase 4 (CDK4). Immunostimulatory activity of andrographolide is evidenced by increased proliferation of lymphocytes and production of interleukin-2. Andrographolide also enhanced the tumor necrosis factor-alpha production and CD marker expression, resulting in increased cytotoxic activity of lymphocytes against cancer cells, which may contribute for its indirect anticancer activity. The in vivo anticancer activity of the compound is further substantiated against B16F0 melanoma syngenic and HT-29 xenograft models. These results suggest that andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential for being developed as a cancer therapeutic agent.
PMID: 14641821 [PubMed - indexed for MEDLINE]

Anticancer and immunostimulatory compounds from Andrographis paniculata.
Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S.
Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad 500050, India.
Andrographis paniculata extract is traditionally used as a medicine to treat different diseases in India, China and Southeast Asia. In the present study, we evaluated the anticancer and immunomodulatory activity of the methanolic extract of Andrographis paniculata in human cancer and immune cells. The methanolic extract of Andrographis paniculata was fractionated into dichloromethane, petroleum ether and aqueous extracts and screened for bioactivity. Our results indicate that the dichloromethane fraction of the methanolic extract retains the active compounds contributing for both the anticancer and immunostimulatory activity. Dichloromethane fraction significantly inhibits the proliferation of HT-29 (colon cancer) cells and augments the proliferation human peripheral blood lymphocytes (HPBLs) at low concentrations. On further fractionation of the dichloromethane extract we could isolate three diterpene compounds, i.e. [1] andrographolide, [2] 14-deoxyandrographolide and [3] 14-deoxy-11,12-didehydroandrographolide. Andrographolide showed anticancer activity on diverse cancer cells representing different types of human cancers. Whereas all the three molecules showed enhanced proliferation and interleukin-2 (IL-2) induction in HPBLs.
PMID: 15138014 [PubMed - indexed for MEDLINE]

Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata
Sriram Rajagopal1, R. Ajaya kumar1, Dhanvanthri S. Deevi1, Chitkala Satyanarayana1, and R. Rajagopalan1
Andrographis paniculata plant extract is known to possess a variety of pharmacological activities. Andrographolide, the major constituent of the extract is implicated towards its pharmacological activity. We studied the cellular processes and targets modulated by andrographolide treatment in human cancer and immune cells. Andrographolide treatment inhibited the in vitro proliferation of different tumor cell lines, representing various types of cancers. The compound exerts direct anticancer activity on cancer cells by cellcycle arrest at G0/G1 phase through induction of cellcycle inhibitory protein p27 and decreased expression of cyclindependent kinase 4 (CDK4). Immunostimulatory activity of andrographolide is evidenced by increased proliferation of lymphocytes and production of interleukin2. Andrographolide also enhanced the tumor necrosis factor production and CD marker expression, resulting in increased cytotoxic activity of lymphocytes against cancer cells, which may contribute for its indirect anticancer activity. The in vivo anticancer activity of the compound is further substantiated against B16F0 melanoma syngenic and HT29 xenograft models. These results suggest that andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential for being developed as a cancer therapeutic agent.

Taraxasterol
Taraxasterol is extracted from Taraxacum mongolicum (Pu Gong Ying), a traditional Chinese herb used as a bactericide for 'clearing toxic heat'. Taraxasterol is anti-bacterial, anti-viral, immune enhancing and hepatopretective. It increases peripheral lymphoblast transformation rate.
Taraxasterol

Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants.
Sengul M, Yildiz H, Gungor N, Cetin B, Eser Z, Ercisli S.
Crude extracts from Inula aucherana, Fumaria officinalis, Crocus sativus, Vicum album, Tribulus terestris, Polygonatum multiflorum, Alkanna tinctoria and Taraxacum officinale were screened for their in vitro antioxidant and antimicrobial properties. Total phenolic content of extracts from these plants were also determined. beta-carotene bleaching assay and Folin-Ciocalteu reagent were used to determine total antioxidant activity and total phenols of plant extracts. Antimicrobial activity was determined by using disk diffusion assay. Antioxidant activity and total phenolic content varied among plants used and Viscum album and Crocus sativus had the highest antioxidant (82.23%) and total phenolic content (42.29 mgGAE/g DW), respectively. The methanol extracts from Vicum album and Alkanna tinctoria showed antimicrobial activity against 9 out of 32 micro-organisms, however extract from Inula aucherana showed antimicrobial activity against 15 out of 32 micro-organisms. The results provided evidence that the studied plant might indeed be potential sources of natural antioxidant and antimicrobial agents. Pak J Pharm Sci. 2009 Jan;22(1):102-6.

Anti-inflammatory activity of Taraxacum officinale.
Jeon HJ, Kang HJ, Jung HJ, Kang YS, Lim CJ, Kim YM, Park EH.
Taraxacum officinale has been widely used as a folkloric medicine for the treatment of diverse diseases. The dried plant was extracted with 70% ethanol to generate its ethanol extract (TEE). For some experiments, ethyl acetate (EA), n-butanol (BuOH) and aqueous (Aq) fractions were prepared in succession from TEE. TEE showed a scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, a diminishing effect on intracellular reactive oxygen species (ROS) level, and an anti-angiogenic activity in the chicken chorioallantoic (CAM) assay. In the carrageenan-induced air pouch model, TEE inhibited production of exudate, and significantly diminished nitric oxide (NO) and leukocyte levels in the exudate. It also possessed an inhibitory effect on acetic acid-induced vascular permeability and caused a dose-dependent inhibition on acetic acid-induced abdominal writhing in mice. Suppressive effects of TEE on the production of NO and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide
(LPS)-stimulated macrophages were also assessed. Among the fractions, the n-butanol fraction (BuOH) was identified to be most effective in the CAM assay. Collectively, Taraxacum officinale contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities through its inhibition of NO production and COX-2 expression and/or its antioxidative activity. J Ethnopharmacol. 2008 Jan 4;115(1):82-8.

Taraxasterol and beta-sitosterol: new naturally compounds with chemoprotective/chemopreventive effects.
Ovesna Z, Vachalkova A, Horvathova K.
Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic. zdenka.ovesna@savba.sk
Substantial attention has been given to primary cancer prevention in daily life. Dietary factors are through to contribute to as much as one-third of the factors influencing the development of cancer. Ones of the components of a plant-based diet are beta-sitosterol and taraxasterol, compounds attracting our specific attention. This review summarises the biological activities of presented phytosterols (anti-inflammatory, cholesterol-lowering, anti-microbial, anti-bacterial, anti-fungal effects). Our interest has been focused especially on their anti-tumour and chemopreventive activity. They have been shown experimentally to inhibit colon and breast cancer development. They act at various stages of tumour development, including inhibition of tumourigenesis, inhibition of tumour promotion, and induction of cell differentiation. They effectively inhibit invasion of tumour cells and metastasis. With regard to toxicity, no obvious side effects of phytosterols have been observed in studies to date, with the exception of individuals with phytosterolemia. The exact mechanism by which dietary phytosterols act is not fully understood. However, some mechanisms have been offered. Therefore, they have a bright future in clinical application.
Biol Pharm Bull 1999 Jun;22(6):602-5

Studies on immunopotentiating activities of antitumour polysaccharide from aerial parts of Taraxacum platycarpum.
Jeong JY, Chung YB, Lee CC, Park SW, Lee CK
College of Pharmacy, Kyungsung University, Pusan, Korea.
The polysaccharide fraction from Taraxii Herba showed potent immuno-potentiating activities with anti-tumour activities. The fraction having small amount of protein inhibited the growth of solid tumour and increased peritoneal exudate cells and immuno-organ weights in normal mice, and also increased hypersensitivities in tumour bearing mice.
PMID: 10319124, UI: 99252682


Extract of Flos Lonicera (Jin Yin Hua) w/ Standardised Chlorogenic acid
Jin Yin Hua, a herb traditionally used in China as an anti-pyretic, anti-inflammatory and anti-microbial has recently been shown to have significant anti-malignancy properties. The herb is been mainly used for upper respiratory tract infections as well as tonsillitis and acute laryngitis. During influenza outbreaks Jin Yin Hua is used as a preventative according to the 'Shanghai Journal of Chinese Medicine and Herbology' 1983; 9; 27
Chlorogenic acid
Chlorogenic acid is a phenolic natural product isolated from the leaves and fruits of dicotyledonous plants, including the coffee bean. Structurally, chlorogenic acid is the ester of caffeic acid with the 3-hydroxyl group of quinic acid. Chlorogenic acid is an important factor in plant metabolism. It is also an antioxidant and an inhibitor of the tumor promoting activity of phorbol esters.1 2 Chlorogenic acid, at concentrations as high as 100 œÌM, does not inhibit the 5-lipoxygenase activity of ionophore-stimulated human polymorphonuclear leukocytes. 3
Chlorogenic acid can be used as anti-infectious active ingredient, it has wide anti-virus, anti-bacteria effects, and has relatively lower toxicity and side-effects. It has obvious anti-infectious effects, and does not like to lead Anti-microbial Resistance.

1 Huang, M.T., Smart, R.C., Wong, C., et al. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 48, 5941-5946 (1988).
2 Conney, A.H., Lysz, T., Ferraro, T., et al. Inhibitory effect of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. Adv Enzyme Regul 31, 385-396 (1991).
3Kimura, Y., Okuda, H., Okuda, T., et al. Studies on the activities of tannins and related compounds, X. Effects of coffee tannins and related compounds on arachidonate metabolism in human polymorphonuclear leukocytes. J Nat Prod 50, 392-399 (1987).

Chlorogenic acid found in the flower of the Lonicera plant, may act as an anti-microbial agent. Derivatives of chlorogenic acid displayed antiviral and antibacterial properties against herpes simplex virus and Escherichia coli respectively. Chlorogenic acid has been shown to inhibit RNA-dependent DNA polymerase (an enzyme needed for viral replication). Flos Lonicera extract has been helpful in the treatment of retroviruses, Human Immuno-Deficiency virus).
The ability of chlorogenic acid to stop free radical processes makes it an effective antioxidant.
In a study that artificially induced diabetes in rats, dried extracts of Flos Lonicera were administered orally for 4 days. Plasma levels of glucose were shown to consistently drop approximately 26% at two different stages of diabetes. It is speculated that chlorogenic acid inhibits the action of the enzymes responsible for hepatic glucose production and /or output into the bloodstream. This inhibition may be useful for the reduction of inappropriately high rates of glucose output often found in non-insulin-dependent diabetes. Interestingly, in the same experiment cited above, chlorogenic acid also exhibited blood lipid lowering properties. When administered in a single dose, extracts of Flos Lonicera were effective in lowering triglyceride concentrations in both normolipidemic and hyperlipidemic animals.
The extracts of Flos Lonicera may prove to be a viable alternative or adjunct to conventional treatments for microbial infections, high cholesterol, and diabetes.

Inhibition of activator protein-1, NF-kappaB, and MAPKs and induction of phase 2 detoxifying enzyme activity by chlorogenic acid.
Feng R, Lu Y, Bowman LL, Qian Y, Castranova V, Ding M.
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet. The antioxidant and anticarcinogenic properties of chlorogenic acid have been established in animal studies. However, little is known about the molecular mechanisms through which chlorogenic acid inhibits carcinogenesis. In this study, we found that chlorogenic acid inhibited the proliferation of A549 human cancer cells in vitro. The results of the soft agar assay indicated that chlorogenic acid suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells in a dose-dependent manner. Pretreatment of JB6 cells with chlorogenic acid blocked UVB- or TPA-induced transactivation of AP-1 and NF-kappaB over the same dose range. At low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2-terminal kinases, p38 kinase, and MAPK kinase 4 induced by UVB/12-O-tetradecanoylphorbol-13-acetate, yet higher doses were required to inhibit extracellular signal-regulated kinases. Chlorogenic acid also increased the enzymatic activities of glutathione S-transferases (GST) and NAD(P)H: quinone oxidoreductase. Further studies indicated that chlorogenic acid could stimulate the nuclear translocation of Nrf2 (NF-E2-related factor) as well as subsequent induction of GSTA1 antioxidant response element (ARE)-mediated GST activity. The phosphatidylinositol 3-kinase pathway might be involved in the activation of Nrf2 translocation. These results provide the first evidence that chlorogenic acid could protect against environmental carcinogen-induced carcinogenesis and suggest that the chemopreventive effects of chlorogenic acid may be through its up-regulation of cellular antioxidant enzymes and suppression of ROS-mediated NF-kappaB, AP-1, and MAPK activation.


 
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