Basic pharmacological mechanisms and clinical evidence of the efficacy of hochuekkito against infectious diseases and its potential for use against COVID‐19

Abstract

Background Hochuekkito extract (HET) has multiple effects through the digestive and immune systems, including for acute viral infection and chronic inflammation. We review basic pharmacological and clinical researches of HET and discuss the effects of HET against the pandemic COVID‐19. Methods We reviewed pharmacological studies from 1996 to 30 April 2020 that used experimental animals orally treated with HET and randomized controlled trials (RCTs) from 2000 to 30 April 2020. Results Altogether, 64 pharmacological studies reported immuno‐stimulatory effects against infection and cancer, immuno‐modulative effects against allergy and some inflammatory diseases, and ameliorating effects against exhaustion and frailty. Nine RCTs showed improvement of pulmonary Mycobacterium avium complex disease on chest X‐ray; improved systemic inflammation, nutrition, and quality of life of patients with chronic obstructive pulmonary disease and a decrease in the number getting common cold and exacerbations; reduction of soluble interleukin‐2 receptor and the serum cortisol concentration of postoperative patients; a reduction of the incidence of inflammatory complications and C‐reactive protein elevation after cerebrovascular disease; a reduction of the volume of steroid and tacrolimus during the treatment of atopic dermatitis; a healing effect for intractable chronic wounds; improvement of the physical status of elderly weak patients; and improvement of the fatigue level of cancer patients. Conclusion CODIV‐19 is characterized by high risk for the aged and people with other disease complications, cytokine hyperactivity in the severe stage, and sequelae in the recovery stage. Considering the immune‐stimulative/modulative effects of HET on inflammatory conditions and against exhaustion and frailty, it may be useful for prevention, treatment, and recovery from COVID‐19.

Prevention and Recovery of COVID-19 Patients With Kampo Medicine: Review of Case Reports and Ongoing Clinical Trials

“…The contribution and prospects of the present projects on Kampo medicine and its efficacy as a COVID-19 treatment are as follows: • Kampo medicine may act on viruses, human tissues, and organs via multiple mechanisms that differ from those of other drugs being developed in Western medicine ( Arita et al, 2020 ; Takayama et al, 2020b ). • Kampo medicines for common cold are well established; their possible side effects are generally known and safety information has already been acquired ( AuthorAnonymous, 2005 ; Kubo et al, 2013 ; Shimamoto et al, 2014 ; Takayama et al, 2017 ; Arai et al, 2018 ; Takayama et al, 2018 ; Takayama et al, 2020d ).…”

“…• Kampo medicine may act on viruses, human tissues, and organs via multiple mechanisms that differ from those of other drugs being developed in Western medicine ( Arita et al, 2020 ; Takayama et al, 2020b ).…”

“…Furthermore, the efficacy of the vaccines may be reduced if SARS-CoV-2 persistently and consistently undergoes mutations (Awadasseid et al, 2021;Lauring and Hodcroft 2021). The possible mechanisms of the preventive effect of hochuekkito (bu Zhong yi qi tang) against COVID-19 have reported by Takayama et al (Takayama et al, 2020b). Thus, clinical trials are being conducted to assess the efficacy of Kampo medicine for preventing COVID-19.…”

Hochuekkito can Prevent the Colonization of Methicillin-Resistant Staphylococcus aureus in Upper Respiratory Tract of Acute Stroke Patients

“…HET includes 10 crude drugs: JP Astragalus root, JP Atractylodes lancea rhizome, JP ginseng, JP Japanese angelica root, JP Bupleurum root, JP jujube, JP Citrus unshiu peel, JP Glycyrrhiza , JP Cimicifuga rhizome, and JP ginger. The pharmacological mechanism of action is likely to be complex because HET includes multiple pharmacologically active substances; however, its immuno-stimulatory effects against infection, immuno-modulatory effects against inflammation, and ameliorative effects against exhaustion and frailty have been reported in pharmacological studies and clinical studies ( Takayama et al, 2020b ). To prevent MRSA colonization, a good level of consciousness, ability to self-administer the oral intake, appropriate nutrition as well as innate immunity, and contact transmission are important.…”

“…HET is widely used for the relief of impaired constitution during the recovery from diseases, fatigue, malaise, and anorexia in the national health insurance system; it has also been introduced into some clinical practice guidelines in Japan ( Takayama and Iwasaki, 2017 ; Takayama et al, 2018 ; Takayama et al, 2020a ). HET is a multifunctional drug composed of 10 crude drugs, and it has been documented to promote appetite, support nutrition, and have anti-infection and anti-inflammatory properties ( Takayama et al, 2020b ). These effects can help prevent colonization in a compromised host.…”