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Polymodal K⁺ channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

ABSTRACT: Pain and inflammation contribute immeasurably to reduced quality of life, yet modern analgesic and anti-inflammatory therapeutics can cause dependence and side effects. Here, we screened 1444 plant extracts, prepared primarily from native species in California and the United States Virgin Islands, against two voltage-gated K⁺ channels - T-cell expressed Kv1.3 and nociceptive-neuron expressed Kv7.2/7.3. A subset of extracts both inhibits Kv1.3 and activates Kv7.2/7.3 at hyperpolarized potentials, effects predicted to be anti-inflammatory and analgesic, respectively. Among the top dual hits are witch hazel and fireweed; polymodal modulation of multiple K⁺ channel types by hydrolysable tannins contributes to their dual anti-inflammatory, analgesic actions. In silico docking and mutagenesis data suggest pore-proximal extracellular linker sequence divergence underlies opposite effects of hydrolysable tannins on different Kv1 isoforms. The findings provide molecular insights into the enduring, widespread medicinal use of witch hazel and fireweed and demonstrate a screening strategy for discovering dual anti-inflammatory, analgesic small molecules.

SUBMITTER: Manville RW

PROVIDER: S-EPMC11358443 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Polymodal K<sup>+</sup> channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Manville Rían W RW Yoshimura Ryan F RF Yeromin Andriy V AV Hogenkamp Derk D van der Horst Jennifer J Zavala Angel A Chinedu Sonia S Arena Grey G Lasky Emma E Fisher Mark M Tracy Christopher R CR Othy Shivashankar S Jepps Thomas A TA Cahalan Michael D MD Abbott Geoffrey W GW

Communications biology 20240828 1

Pain and inflammation contribute immeasurably to reduced quality of life, yet modern analgesic and anti-inflammatory therapeutics can cause dependence and side effects. Here, we screened 1444 plant extracts, prepared primarily from native species in California and the United States Virgin Islands, against two voltage-gated K<sup>+</sup> channels - T-cell expressed Kv1.3 and nociceptive-neuron expressed Kv7.2/7.3. A subset of extracts both inhibits Kv1.3 and activates Kv7.2/7.3 at hyperpolarized ...[more]

PMID: 39198706

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Project description:SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

Dataset Information

Polymodal K⁺ channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Publications

Polymodal K<sup>+</sup> channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

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Polymodal K+ channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Publications

Polymodal K<sup>+</sup> channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Polymodal K⁺ channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.