Adaptogens are natural stress-protective compounds or plant extracts that increase the adaptability, resilience, survival and “the state of non-specific resistance” to harmful factors, including bacterial and viral pathogens, explain Alexander Panossian, founder of Phytomed AB, and Thomas Brendler, CEO, PlantaPhile.
More than 100 species of botanicals have been reported to have adaptogenic activity; however, only a few have been shown to exhibit multitarget effects on the neuroendocrine-immune system by triggering an adaptive stress response, including
- stimulating cellular and organismal defence systems
- activating intracellular and extracellular adaptive signalling pathways
- the expression of stress-activated proteins that results in the transient change of protection or repair functions
- increased non-specific resistance and adaptation to stress.1
These are, eleuthero (Eleutherococcus senticosus), ginseng (Panax spp.), rhodiola (Rhodiola rosea), schisandra (Schisandra chinensis), ashwagandha (Withania somnifera) and andrographis (Andrographis paniculata).
Acute viral infections have four distinct stages: infection, viral replication, escalating inflammation and pathogenic inflammation. In the initial infection phase, there are numerous interactions between components of the host’s defence system and the viral pathogen — genomic, transcriptomic, proteomic, metabolomic and macrobiotic.2
Consequently, the effective prevention or treatment of a viral infection requires therapeutic intervention that affects the innate and adaptive immune system, phases I–III metabolising enzymes involved in detoxifying and repair systems, as well as the virus’ lifecycle and proliferation.3
Preclinical evidence
Preclinical trials on extracts or isolated constituents from andrographis, eleuthero, ginseng, rhodiola, schisandra and ashwagandha have shown direct viricidal effects on various strains of influenza and rhinovirus, specific antiviral actions (including the inhibition of non-structural proteins involved in the replication of SARS virus) and indirect non-specific antiviral actions via activation innate immunity, anti-inflammatory effects, detoxification and the repair of cellular and tissue damage induced by oxidative stress, as well as other effects of potential relevance in the progression of viral infections (see Figure 1 for details).3
Figure 1. Schematic diagram of various phases of immune and inflammatory responses to SARS-CoV-2 infection and stages of COVID-19 progression with (highlighted in green color) and without (highlighted in red color) considering potential effects of adaptogenic plants on prevention, infection, inflammation, and recovery phases of viral infection
Key elements of innate immunity stimulation are the activation of the first-line defence response followed by the inhibition of NF-κB and inflammation mediated by proinflammatory cytokines.
Important features of adaptogens are their beneficial effects on detoxification and repair processes, leading to recovery and increased survival in virus-induced oxidative stress.
Key to this is the activation of the antioxidant NRf2-mediated oxidative stress response signalling pathway, the production of detoxification enzymes, the activation of molecular chaperon Hsp70 — which mediates cytoprotectant and repair processes — and the activation of the melatonin signalling pathway to regulate homeostasis.4
Clinical trial evidence
Adaptogens have been subject to numerous clinical trials. Although these are not specific to SARS-CoV-2, the available clinical data provide support for the hypothesis that adaptogens may be beneficial in all stages of viral infections.
A meta-analysis of andrographis clinical trials (including more than 7000 patients) demonstrated improved cough and sore throat and reduced the duration of these and other related respiratory symptoms.5
Other studies indicated that andrographis at a daily dose of 1.2 g reduced the intensity of symptoms and signs of rhinitis, sinus pain and headache, when compared with a placebo.3
Much of the research on eleuthero is from observational studies done in the Soviet Union during the 1970s, with studies involving more than 4500 subjects.
In addition to showing the improvement of performance under stress, cardiovascular and pulmonary disorders, trials indicated that eleuthero given prophylactically can reduce influenza mortality rates and typical complications, such as pneumonia, bronchitis and otitis media. Positive effects of eleuthero were seen in both adults and children.3
The adaptogenic effects of rhodiola have been well-established in clinical trials and has demonstrated utility in specific pulmonary indications. As an adjunctive therapy in chronic obstructive pulmonary disease, rhodiola significantly improved tidal breathing and ventilation efficiency.
A significant decrease in acute respiratory distress syndrome complications was observed in patients preventively treated for acute lung injury caused by post-traumatic/inflammatory and thoracic-cardiovascular operations.3,6
Numerous clinical investigations on schisandra have confirmed that in viral respiratory tract infections, it targets viral RNA synthesis and replication, and stimulates innate and adaptive immunity. Trials have also demonstrated improvement in chemotherapy induced immunosuppression, COPD and fatigue.7,3
A review of 30 human ashwagandha clinical trials indicated its safety and efficacy in subclinical hypothyroidism, chronic stress, insomnia, anxiety and cognitive impairment, among others.8
Adaptogenic effects were studied in three clinical trials, one of which reported significantly increased oxygen consumption, maximum velocity and average absolute and relative power under exercise conditions with ashwagandha supplementation, an outcome that may be relevant in convalescence from respiratory disease.3
Reviews of clinical trials on ginseng species on immune response to respiratory tract infections indicated significant evidence for the immunomodulatory activity of ginseng. The studies also demonstrated that ginseng elicited a reduction in cytokine levels, decreased the severity of oxidative stress, reduced the duration and frequency of symptoms and demonstrated potential for prevention of respiratory infections.3,9,10
Multiple clinical trials on a fixed combination of andrographis and eleuthero confirmed a significant relief of symptoms of uncomplicated respiratory tract infections caused by the common cold. Studies showed relief of sinusitis, headache, myalgia, nasal congestion and nasal secretion, and an accelerated recovery time.3
Discussion
The multitarget effects of adaptogens on the neuroendocrine-immune system make them a potentially important preventive and adjunctive treatment for SARS-CoV-2 infections. They provide baseline support through their immunomodulatory, immunostimulatory and antioxidant effects through all phases.
Adaptogens help to combat infection through their specific and non-specific antiviral properties, alleviate escalating inflammation through their anti-inflammatory effects, as well as their capacity to repair oxidative stress-induced injuries in compromised cells and tissues, and address secondary disease states and comorbidities through various infection-related activities.
References
- A. Panossian, “Understanding Adaptogenic Activity: Specificity of the Pharmacological Action of Adaptogens and Other Phytochemicals,” Ann. NY Acad. Sci. 1401(1), 49–64 (2017).
- R. Yang, et al., “Chemical Composition and Pharmacological Mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction Against Coronavirus Disease 2019 (COVID-19): In Silico and Experimental Study,” Pharmacol. Res. 157, 104820 (2020).
- A. Panossian and T. Brendler, “The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections,” Pharmaceuticals 13(9), 236 (2020).
- A. Panossian, et al., “Novel Molecular Mechanisms for the Adaptogenic Effects of Herbal Extracts on Isolated Brain Cells Using Systems Biology,” Phytomedicine 50, 257–284 (2018).
- X.Y. Hu, et al., “Andrographis paniculata (Chuan Xin Lian) for Symptomatic Relief of Acute Respiratory Tract Infections in Adults and Children: A Systematic Review and Meta-Analysis,” PLoS One 12(8): e0181780 (2017).
- H. Tao, et al., “Rhodiola Species: A Comprehensive Review of Traditional Use, Phytochemistry, Pharmacology, Toxicity and Clinical Study,” Medicinal Research Reviews 39(5), 1779–1850 (2019).
- A. Nowak, et al., “Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition: A Review of Current Knowledge and Therapeutic Perspectives,” Nutrients 11(2), 333 (2019).
- N. Tandon and S.S. Yadav, “Safety and Clinical Effectiveness of Withania somnifera (Linn.) Dunal Root in Human Ailments,” J. Ethnopharmacol. 255, 112768 (2020).
- H. Iqbal and D.K. Rhee, “Ginseng Alleviates Microbial Infections of the Respiratory Tract: A Review,” J. Ginseng Res. 44(2), 194–204 (2020).
- Z.A. Ratan, et al., “Adaptogenic Effects of Panax ginseng on Modulation of Immune Functions,” J. Ginseng Res. (2020): https://doi.org/10.1016/j.jgr.2020.09.004.