Botanical immunodrugs: scope and opportunities

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Abstract

Traditional knowledge-driven bioprospecting offers access to multiple targets that can provide a safer and more cost-effective platform for newer scaffolds to facilitate drug discovery.

Abstract

Modulation of the immune system can be addressed through a variety of specific and non-specific approaches. Many agents of synthetic and natural origin have stimulatory, suppressive or regulatory activity. There is growing evidence that drugs or biological agents capable of modulating single pathways or targets are of limited value as immune-related therapies. Systems biology approaches are now gaining more interest compared with monovalent approaches, which can be of limited benefits with complications. This has stimulated interest in the use of ‘cocktails’ of immunodrugs to restore immunostasis. Botanicals are chemically complex and diverse and could therefore provide appropriate combinations of synergistic moieties useful in drug discovery. Here, the importance of traditional medicine in natural product drug discovery related to immunodrugs is reviewed.

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Most cited references 90

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Inferences, questions and possibilities in Toll-like receptor signalling.

Bruce Beutler (2004)

The Toll-like receptors (TLRs) are the key proteins that allow mammals--whether immunologically naive or experienced--to detect microbes. They lie at the core of our inherited resistance to disease, initiating most of the phenomena that occur in the course of infection. Quasi-infectious stimuli that have been used for decades to study inflammatory mechanisms can activate the TLR family of proteins. And it now seems that many inflammatory processes, both sterile and infectious, may depend on TLR signalling. We are in a good position to apply our understanding of TLR signalling to a range of challenges in immunology and medicine.

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Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group.

R Maini, E W St Clair, F Breedveld … (1999)

Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate. In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group. During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate.

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Drugs from the deep: marine natural products as drug candidates.

Burkhard Haefner (2003)

In recent years, marine natural product bioprospecting has yielded a considerable number of drug candidates. Most of these molecules are still in preclinical or early clinical development but some are already on the market, such as cytarabine, or are predicted to be approved soon, such as ET743 (Yondelis). Research into the ecology of marine natural products has shown that many of these compounds function as chemical weapons and have evolved into highly potent inhibitors of physiological processes in the prey, predators or competitors of the marine organisms that use them. Some of the natural products isolated from marine invertebrates have been shown to be, or are suspected to be, of microbial origin and this is now thought to be the case for the majority of such molecules. Marine microorganisms, whose immense genetic and biochemical diversity is only beginning to be appreciated, look likely to become a rich source of novel chemical entities for the discovery of more effective drugs.

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Author and article information

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Bhushan Patwardhan

Journal

Journal ID (nlm-ta): Drug Discov Today

Journal ID (iso-abbrev): Drug Discov. Today

Title: Drug Discovery Today

Publisher: Elsevier Ltd.

ISSN (Print): 1359-6446

ISSN (Electronic): 1878-5832

Publication date PMC-release: 2 April 2005

Publication date (Print): 1 April 2005

Publication date (Electronic): 2 April 2005

Volume: 10

Issue: 7

Pages: 495-502

Affiliations

Bioprospecting Laboratory, Interdisciplinary School of Health Sciences, University of Pune, Pune - 411007, India

Article

Publisher ID: S1359-6446(04)03357-4

DOI: 10.1016/S1359-6446(04)03357-4

PMC ID: 7128543

PubMed ID: 15809195

SO-VID: efa841ea-9f96-47c1-9438-66c6cb762410

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Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Botanical immunodrugs: scope and opportunities

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RNA drug delivery

Most cited references 90

Inferences, questions and possibilities in Toll-like receptor signalling.

Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group.

Drugs from the deep: marine natural products as drug candidates.

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