Herbs And Phytochemicals: Aqueous Root Extract Of Withania Somnifera Ameliorates Lung Inflammation Caused By COVID-19!

Herbs And Phytochemicals: The COVID-19 pandemic has had a profound impact on global health in the last three years, affecting millions of people worldwide. This highly contagious virus has a life-threatening impact, particularly on individuals with pre-existing health conditions, such as respiratory, cardiac, and metabolic complications. Survivors of the virus often experience a high prevalence of aberrant airway injuries, including pneumonia, bronchitis, and acute respiratory distress syndrome (ARDS).


                                                Withania somnifera 
 
One of the major contributors to the severity of COVID-19 cases is hyper-inflammation, leading to a cytokine storm characterized by the excessive production of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). These cytokines can cause severe organ damage and even lead to fatalities in severe cases. As a result, managing inflammation in COVID-19 patients has been a significant challenge.
 
Corticosteroids, such as dexamethasone, have been commonly prescribed to combat inflammation in COVID-19 patients due to their potent anti-inflammatory properties. However, prolonged use of corticosteroids in patients with comorbidities, such as metabolic diseases and cardiovascular conditions, is associated with safety concerns and potential side effects. As a result, the search for safer and more effective anti-inflammatory therapies for COVID-19 is essential.
 
Withania somnifera, commonly known as Ashwagandha, is a well-known herbal medicine in India. During the pandemic, it gained recognition for its potential to prevent SARS-CoV-2 infection, and it is also renowned for its anti-inflammatory properties. This COVID-19 News report covers a recent study conducted by Translational Health Science and Technology Institute in India and the Drug Research Institute in Lucknow, that shows the potential of the aqueous root extract of Withania somnifera in ameliorating lung inflammation caused by pathogenic infections was explored.
 
This Herbs And Phytochemicals study primarily aimed to investigate the effects of Withania somnifera extract on inflammatory changes in in vitro cell-based assays and mice models of inflammation induced by lipopolysaccharide (LPS), a molecule found in the outer membrane of gram-negative bacteria and a potent trigger of inflammation. The findings of this study suggest the potential utility of Withania somnifera extract in reducing airway inflammation, especially in COVID-19 patients with a high propensity for lung inflammation. The results also highlight the need for further clinical evaluation of this herbal extract.
 
Understanding the Mechanism of Inflammation in COVID-19
To understand the mechanism of the hyper-inflammation seen in COVID-19 patients, researchers have found simi larities between the inflammatory responses triggered by the coronavirus and those induced by Toll-like Receptor 4 (TLR-4) activation. Lipopolysaccharide (LPS), a component of gram-negative bacteria, activates TLR-4 and leads to an increase in the production of pro-inflammatory cytokines, including TNF-α and IL-6.
 
Several anti-inflammatory drugs and herbal medications have been previously tested to inhibit LPS-induced inflammation in both cell-based models and mouse models. Corticosteroids, known for their potent anti-inflammatory properties, are commonly used in COVID-19 patients. However, their unguided use can be harmful in patients with metabolic diseases and other inflammatory conditions due to potential side effects.
 
In response to the challenges presented by COVID-19, the World Health Organization (WHO) recommended a combination of herbal and modern medicine systems to achieve therapeutic benefits with minimal side effects. Ayurveda, one of the world's oldest medical systems, is based on natural remedies derived from plants and traditional knowledge. Withania somnifera, or Ashwagandha, is one of the medicinal plants mentioned in Ayurveda known for its diverse properties, including anti-inflammatory, antiviral, anti-diabetic, neuroprotective, analgesic, anti-tumor, and immunomodulatory effects.
 
The Anti-Inflammatory Potential of Withania somnifera
Recent research has demonstrated the protective effect of the aqueous extract of Withania somnifera roots in experimental models of SARS-CoV-2, T cell differentiation, and neutrophil functions. This extract has been shown to reduce viral load and inflammation. Additionally, Withaferin A (WA) and its derivatives, compounds found in Withania somnifera, have shown promise in the treatment of lung cancer, inhibiting cell adhesion, migration, and invasion in lung cancer cells.
 
Withanolides present in the aqueous extract of Withania somnifera roots have been found to inhibit TLR-4-activated innate inflammatory signals, making it a potential candidate for reducing inflammation. In another study, WA and Withanones were found to inhibit SARS-CoV-2 proteins, highlighting the potential role of Withania somnifera in combatting COVID-19.
 
Given the high prevalence of lung inflammation in COVID-19 patients, researchers aimed to determine whether Withania somnifera extract could inhibit LPS-induced inflammation in lung-derived cell lines and mice models, particularly in a TLR-4-dependent manner.
 
In Vitro and In Vivo Studies
For in vitro studies, LPS-stimulated NCI-H460 and A549 lung-derived cell lines, as well as human peripheral blood mononuclear cells (PBMCs), were used to assess the anti-inflammatory potential of Withania somnifera. The study also examined the impact of Withania somnifera on BALB/c mice challenged with LPS through intranasal administration, which led to increased neutrophil migration in the broncho-alveolar lavage (BAL) fluid and the induction of pro-inflammatory cytokines in lung tissues.
 
The results of these studies were promising:
 
-Withania somnifera extract reduced the levels of LPS-induced increase in pro-inflammatory cytokines in NCI-H460 cells.
 
-Withania somnifera extract reduced the levels of LPS-induced increase in pro-inflammatory cytokines in human PBMCs.
 
-Withania somnifera attenuated the LPS-induced increase in neutrophil counts in the broncho-alveolar lavage (BAL) fluid of BALB/c mice.
 
-Withania somnifera reduced the levels of inflammatory cytokines in the lung tissues of BALB/c mice challenged with LPS.
 
-Withania somnifera ameliorated the LPS-induced lung damage in BALB/c mice in a 4-day study.
 
The results suggest that Withania somnifera extract has the potential to combat lung inflammation in both in vitro and in vivo models, and its effectiveness should be further evaluated in clinical settings.
 
The Importance of Inflammation Management
Inflammation is a vital response that helps the body defend itself against injury and infection. However, uncontrolled or chronic inflammation can lead to tissue damage and the loss of tissue homeostasis. COVID-19 has brought to light the critical role of inflammation in respiratory complications, making it essential to identify therapies that can alleviate lung inflammation in affected patients.
 
The World Health Organization (WHO) has issued guidelines for the treatment of COVID-19 patients, recommending the use of corticosteroids for hospitalized patients with severe infections. However, there is no data to support the use of systemic corticosteroids in non-hospitalized COVID-19 patients. The potential side effects of corticosteroids, such as hyperglycemia, neuropsychiatric symptoms, and secondary infections, make their use without clinical supervision risky.
 
Ayurveda, an ancient traditional medicinal system originating from India, offers a wide range of remedies based on plants and natural resources. Withania somnifera, known as Ashwagandha, is one of the many medicinal plants mentioned in Ayurveda for its therapeutic potential. It has been studied extensively and has shown various health benefits, including its anti-inflammatory properties.
 
The anti-inflammatory activity of Withania somnifera extract and its phytoconstituents has been demonstrated in various studies. It has been shown to inhibit the release of nitric oxide, a pro-inflammatory molecule, and has been effective in managing chronic obstructive pulmonary disease (COPD) patients. Previous research has also demonstrated its antiviral and immunomodulatory properties, making it effective in mitigating pulmonary pathology in COVID-19 models.
 
Withania somnifera has been found to be safe and without herb-drug interactions, making it a promising candidate for the management of inflammation in COVID-19 and other respiratory conditions.
 
Conclusion
The COVID-19 pandemic has underscored the need for effective and safe anti-inflammatory therapies, particularly in patients with pre-existing health conditions. Withania somnifera, or Ashwagandha, is an herbal remedy with a long history of use in Ayurvedic medicine and has demonstrated significant potential in reducing inflammation in in vitro and in vivo models.
 
The results of the studies conducted on Withania somnifera extract provide compelling evidence of its effectiveness in reducing pro-inflammatory cytokines and neutrophil counts in the lungs. This suggests its potential utility in managing lung inflammation, a common concern in COVID-19 patients and other respiratory disorders.
 
Further clinical evaluations are needed to validate the findings of these studies and explore the full potential of Withania somnifera as a safe and effective anti-inflammatory therapy. With ongoing research, herbal remedies like Withania somnifera may offer a promising solution to combat inflammation in COVID-19 patients, with the added benefit of minimal side effects compared to traditional corticosteroids. As we continue to grapple with the challenges of the pandemic, the exploration of herbal medicines and phytochemicals could open up new avenues for treating inflammatory conditions and enhancing public health.
 
The study findings were published in the peer reviewed journal: Frontiers In Pharmacology.
https://www.frontiersin.org/articles/10.3389/fphar.2023.1139654/full
 
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