Withania somnifera (L.) Dunal as Add-On Therapy for COPD Patients: A Randomized, Placebo-Controlled, Double-Blind Study

Abstract

Background: The current gold-standard therapies for chronic obstructive pulmonary disease (COPD) lack disease-modifying potential and exert adverse side effects. Moreover, COPD patients are at a higher risk of severe outcomes if they get infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of the current epidemic. This is the first study to document clinical research on an adaptogenic and steroidal activity–containing herb as a complementary medicine for COPD treatment.Objective: We aimed to evaluate the efficacy of Withania somnifera (L.) Dunal [Solanaceae] (WS) as an add-on therapy for COPD patients.Methods: A randomized, placebo-controlled, and double-blind clinical study was conducted. A total of 150 patients were randomly assigned to three groups: control, placebo, and WS group. In addition to conventional medicines, WS root capsules or starch capsules were given twice a day to the WS group and the placebo group, respectively. Their lung functioning, quality of life, exercise tolerance, systemic oxidative stress (OS), and systemic inflammation were assessed before and after 12 weeks of intervention. WS root phytochemicals were identified by LC-ESI-MS. The inhibitory activity of these phytochemicals against angiotensin-converting enzyme 2 (ACE-2); the SARS-CoV-2 receptor; myeloperoxidase (MPO); and interleukin-6 (IL-6) was evaluated by in silico docking to investigate the mechanism of action of WS.Results: The pulmonary functioning, quality of life, and exercise tolerance improved, and inflammation reduced notably the most in the WS group. Systemic oxidative stress subsided significantly only in the WS group. Although a minor placebo effect was observed in the SGRQ test, but it was not present in other tests. Withanolides found in the WS roots demonstrated substantial inhibitory activity against the proteins ACE-2, MPO, and IL-6, compared to that of a standard drug or known inhibitor. Moreover, FEV1% predicted had significant correlation with systemic antioxidative status (positive correlation) and malondialdehyde (MDA, negative correlation), suggesting that the antioxidative potential of WS has significant contribution to improving lung functioning.Conclusion: Our study clinically demonstrated that WS root when given along with conventional drugs ameliorated COPD significantly more in comparison to the conventional drugs alone, in GOLD 2 and 3 categories of COPD patients. In silico, it has potent inhibitory activity against SARS-CoV-2 receptor, ACE-2, MPO, and IL-6.

Ashwagandha root extract attenuates inflammation in Oleic acid induced-ALI/ARDS rat model via inhibition of ACE and MAPK signaling pathways

“…This result is consistent with the study showing that the level of MPO increases with the effect of Oleic acid (Ito et al, 2005). Moreover, our finding confirmed the study that the inhibitory activity of Withanolides found in the Ashwagandha roots against the MPO in chronic obstructive pulmonary disease patients (Singh et al, 2022). * denotes significant differences between other studied groups and control (*: p<0.05, **: p<0.01), ε denotes significant differences between other studied groups and the OA group (ε: p<0.05, εε: p<0.01).…”

Modulation of Immunological, Biochemical, and Histopathological Changes of Airway Remodeling by Withania somnifera in an Experimental Model of Allergic Asthma in Rats

“…Chronic airway inflammation in asthma is associated with oxidative DNA damage and lipid peroxidation, which is exacerbated by deficient antioxidant defenses in the airways. In a recent clinical study, oral treatment with 250 mg of WS root capsules for 12 weeks in COPD patients significantly decreased systemic inflammation and oxidative stress and improved lung functioning, quality of life, and exercise tolerance as compared with the placebo group [19]. In line with this result, our study findings showed that pretreatment with WS extract protected against oxidative stress-induced DNA damage in the lung tissue as evidenced by lowered 8-OHdG levels (a marker of oxida-tive stress-induced DNA damage) in lung tissues and BALF in OVA-asthmatic animals.…”

The aqueous root extract of Withania somnifera ameliorates LPS-induced inflammatory changes in the in vitro cell-based and mice models of inflammation

“…W. somnifera, popularly known as Ashwagandha, is one such medicinal plant mentioned in Ayurveda and is known for its antiviral, anti-inflammatory, anti-diabetic, neuroprotective, analgesic, anti-tumor, and immunomodulatory properties ( Fugner, 1973 ; Singh et al, 2015 ; Tiwari et al, 2014 ) including pulmonary hypertension and fibrosis ( Kaur et al, 2015 ). The anti-inflammatory activity of WS extract and its phytoconstituents has been demonstrated in RAW 264.7 cells by the inhibition of LPS-mediated release of nitric oxide following induction of iNOS and COX-2 expression ( Orrù et al, 2023 ) A recently conducted double-blind placebo-controlled clinical trial study ( Singh et al, 2022 ) and recent reviews advocate the benefits of WS extract in the management of COPD patients when given alone or in combination with conventional drugs ( Paul et al, 2021 ; Saggam et al, 2021 ). A previous study from our lab has shown that WS possesses both antiviral and immunomodulatory properties and was effective in mitigating the pulmonary pathology of COVID-19 in the hamster and transgenic mice models ( Rizvi, et al, 2023 ).…”