H1N1 influenza, a subtype of influenza A virus, is an infectious viral illness that causes both upper and, in some cases, lower respiratory tract infections.1 Thymoquinone, the primary active compound in black seed oil (Nigella sativa) used in the traditional medicine of multiple cultures for more than 2,000 years2,3 for a variety of conditions, has been used in treatment of respiratory infections. This article will explore the use of thymoquinone (TQ) for upper respiratory tract infections, including H1N1.

About H1N1

Let’s start with a review of H1N1 influenza infections, which can cause symptoms such as rhinorrhea (i.e., a runny nose), rigors (i.e., feeling cold with shivering), myalgia (i.e., muscle pain), headache, fever, loss of appetite and, possibly, lower respiratory tract disease and gastrointestinal disease. Although rare, H1N1 influenza can lead to acute respiratory distress syndrome and secondary bacterial sepsis. In 2009, a pandemic variant of H1N1, known as “swine flu,” emerged from the recombination of various prior swine, avian and human influenza strains, causing a global pandemic affecting millions of people and impacting industries, including food and tourism.4

The World Health Organization (WHO) reported5 that before the H1N1 pandemic in 2009, the influenza A(H1N1) virus had never been identified as a cause of infections in people. Genetic analyses of this virus have shown that it originated from animal influenza viruses and is unrelated to the human seasonal H1N1 viruses that have been in general circulation among people since 1977. After early reports of influenza outbreaks in North America in April 2009, the new influenza virus spread rapidly around the world. By the time WHO declared a pandemic in June 2009, a total of 74 countries and territories had reported laboratory confirmed infections. Unlike typical seasonal flu patterns, the new virus caused high levels of summer infections in the northern hemisphere, and then even higher levels of activity during cooler months. The new virus also led to patterns of death and illness not normally seen in influenza infections. The H1N1 (2009) virus continues to circulate as a seasonal virus and is included in the vaccines against seasonal influenza.

Thymoquinone and Anti-inflammatory Effects

TQ has an anti-inflammatory and antioxidant properties in several disorders including asthma, bronchitis and influenza. TQ exerts its anti-inflammatory and antioxidant effects via several molecular pathways, including the release of cytokines, and activation of cyclooxygenase-2 (COX2), nuclear factor erythroid 2–related factor 2 (Nrf2), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), nuclear factor kappa-light-chain-enhancer of activated B (NF-Κβ).6 So, what does this have to do with H1N1? Simply that a reduction in inflammation may have a positive impact on respiratory disorders.

The efficacy of TQ in respiratory disorders has been documented.7,8 Administration of TQ in lung damaged rats led to notable sup- pression in the inflammatory responses, with decreased bronchial inflammation and alveolar edema.9 El-Khouly et al. demonstrated that TQ supplementation in bleomycin-stimulated rats decreased pulmonary fibrosis concomitant with NF-kβ activation. TQ also resolved emphysema in the alveoli, concomitant with increased antioxidant activity.10

Likewise, an in-vitro and mouse study11 was conducted in which the additive effects of TQ and vitamin D3 were examined on immune-mediated inflammation of mesenchymal stem cells (MSCs)—found in bone marrow and important for making and repairing skeletal tissues. The results were that TQ significantly decreased the inflammatory cytokine TNFα while improving immune function, both alone and with vitamin D3—which enhanced effects.

So now, let’s look at the effects of thymoquinone from black seed oil on upper-respiratory tract complaints (URTCs)—which might be present in different types of influenza.

Thymoquinone and Upper-respiratory Tract Complaints

A four-week, placebo-controlled, double-blind study12 was conducted to evaluate the effect of 500 mg/day BSO standardized for 3 percent thymoquinone (ThymoQuin, USP grade, black cumin seed oil standardized to 3 percent thymoquinone and Min 1 percent P-Cymene and low free fatty acid (< 1.25 percent)) or placebo on URTCs and psychological mood state in 37 marathon and half-marathon runners. Subjective and objective measures were collected before and after supplementation. Subjects completed the profile of mood state (POMS) psychological assessment and a questionnaire style health log measuring health status and URTCs (subjective measures), as well as provided saliva samples and fecal samples for measurement of cortisol and microbiome balance, respectively (objective measures). Results were that subjects in the ThymoQuin supplementation group reported significantly fewer upper respiratory tract complaints (62 percent lower) and better overall well-being (11 percent improvement), as well as lower cortisol (44 percent less) and superior microbiome diversity (66 percent higher Streptococcus thermophilus, 8 percent higher microbiome composite score) compared to placebo. These results suggest that ThymoQuin black seed oil may improve immune system vigilance and overall well-being following the stress of endurance training and competition.

A placebo-controlled, human clinical study13 was conducted in which the effects of 500 mg of BSO plus 1,500 mg fish oil (providing 1,200 mg omega-3 fatty acids), or placebo were evaluated on upper-respiratory tract complaints (URTCs) and psychological mood state in 35 male and female runners during a four-week supplementation period (three weeks before and one week following a marathon or half-marathon competition). Subjective and objective measures were collected before and after supplementation. Results were that subjects in the supplementation group experienced significantly fewer upper-respiratory tract complaints (URTCs) and better overall well-being, as well as higher ω3 blood levels, lower cortisol and superior microbiome indices, compared to placebo. These results suggest that the combination of BSO plus fish oil may improve immune system vigilance and overall well-being following the stress of endurance training and competition, possibly via improvements in the microbiome and gut-immune-axis.

In a design similar to that the of previously described BSO and fish oil study, this study14 evaluated the effects of a combination of 500 mg BSO and 8 mg astaxanthin on URTCs and psychological mood state in 32 male and female runners or a placebo daily during a four-week supplementation period (three weeks before and one week following a marathon or half-marathon competition). Subjective and objective measures were collected before and after supplementation. Results were that subjects in the supplementation group experienced significantly fewer URTCs and better overall well-being, as well as lower cortisol and superior microbiome indices, compared to placebo. Likewise, these results suggest that the combination of BSO plus astaxanthin may improve immune system vigilance and overall well-being following the stress of endurance training and competition, possibly via improvements in the microbiome and gut-immune-brain-axis.

Thymoquinone and H1N1

This study15 investigated the antiviral efficacy of ThymoQuin black seed oil against the H1N1 virus in MDCK cells (i.e., a cell line frequently used in studies of viral infections, including influenza, due to their susceptibility to various influenza strains16). Two test items, NSQ (ThymoQuin standardized at 3 percent thymoquinone) and NSQL (a blend of ThymoQuin with added lycopene, phytoene, phytofluene and beta-carotene), were evaluated. Utilizing Tamiflu—antiviral drug as a positive control, researchers compared the antiviral activity of NSQ and NSQL (at high, medium and low concentrations) to determine their potential as alternative or complementary treatments for influenza infections. The findings demonstrate that both NSQ and NSQL exhibited significant antiviral activity against the H1N1 virus in MDCK cells. The assay indicated a dose-dependent inhibition of viral replication. At higher concentrations, both NSQ and NSQL showed comparable efficacy to Tamiflu, reducing H1N1 cell viability significantly. Future human studies would help to further validate TQ for this purpose.

Thymoquinone and Other Potential Antiviral Applications

A scientific review article17 examined the potential of thymoquinone against other infections, in consideration of recent pandemics. The authors searched papers on TQ and its effects on different infectious diseases in databases like PubMed, Web of Science, Scopus and Google Scholar, and reviewed them. They indicated that, to date, research suggests that natural products may become a potential therapeutic option for their prodigious antiviral or antimicrobial effects on infectious diseases, and that TQ is known for its beneficial activities against several diseases, including infections. They summarized that results from in-vitro and in-vivo studies indicate that TQ is effective against tuberculosis, influenza, dengue, Ebola, Zika, hepatitis, malaria, HIV and even recent pandemics caused by severe acute respiratory syndrome of coronaviruses (SARS-CoV and SARS-CoV-2).

Conclusion

TQ has anti-inflammatory and antioxidant properties against several respiratory tract disorders and infections, including influenza. Clinical research has demonstrated that TQ has effectiveness against upper-respiratory tract complaints. Furthermore, a cell line study demonstrated that TQ (as ThymoQuin) alone or combined with other nutraceuticals showed comparable antiviral activity against the H1N1 virus. NIE

References

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Gene Bruno, DBM, MHS, Professor Emeritus of Nutraceutical Science, is a writer, educator and a nutraceutical scientist with more than 45 years of experience educating natural product retailers and health care professionals and formulating natural products for dozens of dietary supplement companies. He has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. Bruno also hosts “The Vitamin Professor Podcast” brought to you by VRM Media. He can be reached at [email protected].