Modulation of cytokine expression by traditional medicines: A review of herbal immunomodulators

Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750 Montpelier Road, Laurel, MD 20723, USA. .
Alternative medicine review: a journal of clinical therapeutic (Impact Factor: 3.83). 07/2006; 11(2):128-50.
Source: PubMed


Modulation of cytokine secretion may offer novel approaches in the treatment of a variety of diseases. One strategy in the modulation of cytokine expression may be through the use of herbal medicines. A class of herbal medicines, known as immunomodulators, alters the activity of immune function through the dynamic regulation of informational molecules such as cytokines. This may offer an explanation of the effects of herbs on the immune system and other tissues. For this informal review, the authors surveyed the primary literature on medicinal plants and their effects on cytokine expression, taking special care to analyze research that utilized the multi-component extracts equivalent to or similar to what are used in traditional medicine, clinical phytotherapy, or in the marketplace.
MEDLINE, EBSCO, and BIOSIS were used to identify research on botanical medicines, in whole or standardized form, that act on cytokine activity through different models, i.e., in vivo (human and animal), ex vivo, or in vitro.
Many medicinal plant extracts had effects on at least one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF, and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia, Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple cytokines.
The in vitro and in vivo research demonstrates that the reviewed botanical medicines modulate the secretion of multiple cytokines. The reported therapeutic success of these plants by traditional cultures and modern clinicians may be partially due to their effects on cytokines. Phytotherapy offers a potential therapeutic modality for the treatment of many differing conditions involving cytokines. Given the activity demonstrated by many of the reviewed herbal medicines and the increasing awareness of the broad-spectrum effects of cytokines on autoimmune conditions and chronic degenerative processes, further study of phytotherapy for cytokine-related diseases and syndromes is warranted.

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    • "In vitro studies have shown that the overall pharmacological effects and therapeutic efficacies of medicinal plants often do not derive from a single compound but from several compounds generating synergistic activity. Such findings have led some researchers to propose that multicomponent pharmacological agents that hit multiple targets impact the complex equilibrium of whole cellular networks more favourably than drugs that act on a single target (Williamson, 2001; Spelman et al., 2006 ). Herbalists have known for centuries the value of using a combination of herbal remedies, single extracts and combined extracts to switch on the body's defence mechanisms, self-healing and protective processes (Busia, 2005). "
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    ABSTRACT: South Africa is currently experiencing an increase in the number of traditional medicine preparations which purport to have immune boosting effects. This is largely related to the high prevalence of HIV infections. This study therefore aimed to evaluate the possible immunomodulatory mechanisms of uMakhonya®, one of the widely used commercial immune boosters, using THP-1 monocyte cells. Endotoxin-free doses of uMakhonya® ranging from 1000μg/mL to 10μg/mL were used to evaluate the cytotoxic effects, cell migration, secretion of twelve different chemokines and possible modulation of nuclear factor kappa Beta (NF-κβ) transcriptional activity. This commercial traditional medicine product was shown to induce dose dependent cytotoxicity with high doses significantly (p<0.05) cytotoxic to monocytes (IC50 of 100.08 and 107.68μg/mL for normal and LPS stimulated THP-1 cells respectively) when compared to untreated cells. The lower doses were shown to have no significant (p>0.05) chemo-attractant effects in the cell migration assay. UMakhonya® at these lower and less cytotoxic doses induced a significant (p<0.05) increase in secretion of chemokines in unstimulated THP-1 cells when compared to untreated and cyclosporine treated cells. In LPS-stimulated THP-1 cells only MIP-1β secretion was significantly increased by both 100 and 10μg/mL. In both unstimulated and LPS-stimulated THP-1 cells the lowest dose of uMakhonya® increased transcriptional activity of NF-κβ which may explain the increase in chemokines secretion. Therefore this in vitro study showed that uMakhonya® is cytotoxic at high doses, did not show any chemo-attractant effects and induced significant increases in chemokines secretion. Increased transcriptional activity of NF-κβ in treated cells may contribute to increased chemokines secretion. This study on uMakhonya® should form the benchmark for the research of the high number of related products that are sold commercially in South Africa.
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    • "These results were indicative of the immune boosting properties of Phela [9]. Regarding the immunomodulatory effects of immune boosters, these ATMs alter the activities of the immune system via the dynamic regulation of informational molecules – cytokines, hormones, neurotransmitters, and other peptides [10]. We have also carried out extensive in vitro research experiments on the immunomodulatory effects of ATMs immune boosters and have shown that these products can modulator both inflammatory and anti-inflammatory cytokines and also chemokines. "

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    • "Thus, use of immunostimulatory plant extracts or compounds alone or in combination with existing chemotherapy can lend leishmaniasis therapy a new direction. As immunostimulatory plant fractions are composed of multiple compounds they may impact upon diverse molecular targets to eliminate the parasites thereby reducing the risk of drug resistance (Spelman et al., 2006 and references therein). Plants of Piperaceae family used as sources of ingredients for food spices have been employed in traditional medicines since ancient times. "
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    ABSTRACT: Visceral leishmaniasis (VL) is a life-threatening protozoal infection chiefly impinging the rural and poor population in the tropical and sub-tropical countries. The deadly affliction is rapidly expanding after its association with AIDS, swiftly defying its status of a neglected disease. Despite successful formulation of vaccine against canine leishmaniasis, no licensed vaccine is yet available for human VL, chemotherapy is in appalling state, and the development of new candidate drugs has been painfully slow. In face of lack of proper incentives, immunostimulatory plant preparations owing antileishmanial efficacy bear potential to rejuvenate awful antileishmanial chemotherapy. We have earlier reported profound leishmanicidal activity of Piper nigrum hexane (PNH) seeds and P. nigrum ethanolic (PNE) fractions derived from P. nigrum seeds against Leishmania donovani promastigotes and amastigotes. In the present study, we illustrate that the remarkable anti-promastigote activity exhibited by PNH and PNE is mediated via apoptosis as evidenced by phosphatidylserine externalization, DNA fragmentation, arrest in sub G0/G1 phase, loss of mitochondrial membrane potential and generation of reactive oxygen species. Further, P. nigrum bioactive fractions rendered significant protection to L. donovani infected BALB/c mice in comparison to piperine, a known compound present in Piper species. The substantial therapeutic potential of PNH and PNE was accompanied by elicitation of cell-mediated immune response. The bioactive fractions elevated the secretion of Th1 (INF-γ, TNF-α, and IL-2) cytokines and declined IL-4 and IL-10. PNH and PNE enhanced the production of IgG2a, upregulated the expression of co-stimulatory molecules CD80 and CD86, augmented splenic CD4+ and CD8+ T cell population, induced strong lymphoproliferative and DTH responses and partially stimulated NO production. PNH and PNE were devoid of any hepatic or renal toxicity. These encouraging findings merit further exploration of P. nigrum bioactive fractions as a source of potent and non-toxic antileishmanials.
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