As more data is gathered on COVID-19 and its pathogenesis within the body, it’s becoming clear that inflammatory damage to the cardio-respiratory system, as well as other vital organs, presents life-threatening complication in a wide range of patients. And it’s all driven by an overreactive immune response leading to the deadly cytokine storm.
As practitioners, our tendency may be to fight the virus with antiviral agents and immune boosters. However, as we’re seeing, the essential strategy in treating COVID-19 must include regulation and balancing of the immune system in order to prevent the deadly cytokine storm, while providing critical support to key organs and systems. Specific antiviral agents that also work to balance immune response are essential.
Galectin-3: Master Cytokine Driver
As an upstream “alarmin protein,” Galectin-3 (Gal-3) sits at the headwaters of the inflammatory cascade. Gal-3 is up-regulated when the body is under threat, triggering the release of pro-inflammatory and pro-fibrotic cytokines that drive the inflammatory immune response.
Gal-3 regulation of cytokines happens on several levels: Cytokine transcription and production; cytokine secretion; cytokine diffusion in the extracellular media; cytokine binding to its receptor and receptor mobility; and cytokine/receptor signaling.1
In the vast amount of scientific research, the primary cytokines up-regulated by Gal-3 in sepsis and infections are:
• C-reactive protein (CRP)
• Chemokine ligand 6 (CXC-6; also known as granulocyte chemotactic protein 2)
• Interferon γ-induced protein 10
• Interleukin-1β (IL-1β)
• Interleukin-10 (IL-10)
• Matrix metalloproteinase 9 (MMP-9)
• Tumor necrosis factor-α (TNF-α)
Galectin-3 Inhibition: Dual Actions Against COVID-19
Importantly, a new paper was just released highlighting the role of pharmacologic Gal-3 inhibitors as a possible adjunctive treatment for COVID-19. Published in the journal, PeerJ, this review highlights multiple roles for Gal-3 blockers in addressing the novel virus.
In addition to Gal-3 blockade as a therapeutic approach to prevent deadly cytokine storms, the researchers found that the carbohydrate binding structure of the Gal-3 molecule is nearly identical to the “spike protein” on SARS-CoV-2 viral structures. This viral spike protein is what allows the virus to attach to and infect healthy cells. The researchers posit that the same agents used to block Gal-3 could also be used to block COVID-19 viral replication, by binding its spike protein and preventing entry into cells.2
Most-researched Gal-3 Blocker
The only proven Gal-3 inhibitor available—the original and researched form of modified citrus pectin (MCP)—is shown to down-regulate the expression of Gal-3, TLR4, and MyD88, thereby inhibiting NF-κB-activation. This form of MCP is also shown to decrease the expression of IL-6, IL-1β, IL-18 and TNF-α in an induced myocardial fibrosis and inflammation model.3
Blocking Gal-3 is increasingly known to be of essential value in preventing sepsis and cytokine storms, in addition to addressing chronic inflammatory conditions. With the new findings highlighting the structural similarities between Gal-3 and SARS-CoV-2, Gal-3 blockade becomes a critical strategy.
Today, MCP is earning recognition world-wide as the most-researched Gal-3 blocker and the only proven Gal-3 solution available at this time. By inhibiting Gal-3, MCP demonstrates a multitude of functions resulting in robust clinical endpoints as documented in laboratory data as well as practical application.
Mitigating Cytokine Cardiovascular Damage
As researchers continue to study the effects of this novel virus, findings are emerging that show significant damage to the vascular system in both large arteries and, importantly, microcirculation to the smallest capillaries. One report from the University Hospital Zurich showed inflammation-induced damage to the endothelial cells on the inner lining of blood vessels in infected patients.4
Another study showed tiny blood clots in the pulmonary microvasculature among infected patients.5 This helps to explain why
the novel virus poses such a risk to patients with pre-existing cardiovascular, cardiometabolic and respiratory conditions. It’s estimated that up to 50 percent of patients hospitalized with the virus have a pre-existing heart condition.
Cytokine Storm and Cardiorespiratory Damage
As we’re seeing in the emerging data, the inflammatory immune response to the virus can cause a rapid increase of immune cell signaling cytokines that can overwhelm the body, leading to organ failure and septic shock.
For this reason, it’s critical to balance the immune response by addressing over-active inflammation, encouraging healthy circulation and oxygenation, while also helping to lower the viral load that’s overwhelming the immune system.
Multi-targeted Botanical Formula Helps Balance Key Systems
Research shows that a classical Tibetan herbal formula can offer multitargeted support for these critical functions—promoting a balanced immune response and offering anti-inflammatory, circulation-supportive and direct antiviral benefits.
This Tibetan formula has been extensively studied with 30-plus clinical studies, shown to provide clinically relevant benefits for improved vascular health, immunity and other areas. The formula consists of polyphenol-rich botanicals with harmonizing properties for balanced immune responses and improved cardiovascular and microcirculatory function.
Additional cardio-protective measures including an anti-inflammatory diet and regular cardio exercise help strengthen the heart and vascular system, reduce systemic inflammation and improve immune function.
Honokiol Extract—Antiviral and Immune Modulation
One extensively researched botanical extract is becoming known as a powerful immune-modulatory agent with additional antimicrobial, anti-inflammatory and gene-regulatory benefits: Pure honokiol, an active neoligan extracted from Magnolia officinalis bark. In multiple studies, honokiol is shown to interfere with cytokine signaling at the IL-6/CD44/STAT3 axis. Honokiol has also been shown to favorably modulate numerous signaling pathways to halt pathogenic and inflammatory processes, and regulate cell checkpoints—including P53, “the guardian of the genome.” It also exhibits potent antiviral, antibacterial and anti-fungal properties.
Blocks Cytokine Storm
One study highlighted the regulatory effects of honokiol on the cellular responses of macrophages and monocytes. Investigators analyzed the effects of honokiol with respect to lipopolysaccharide (LPS)-induced cytotoxicity, morphological changes and related events. Honokiol was shown to block LPS-induced cytotoxicity in a dose-dependent manner. Also, honokiol blocked the production of cytotoxic cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α, nitric oxide (NO), and reactive oxygen species (ROS). These results demonstrate the ability of honokiol to modulate various cellular responses managed by macrophages and monocytes.6
Activates SIRT3 for Powerful Defense Against Microbes
Honokiol is well-known to be a SIRT3 activator. SIRT3 is a primary mitochondrial deacetylase protein, with critical roles in mitochondrial function including ATP production, reactive oxygen species (ROS) control and numerous other processes. In immune function, SIRT3 is shown to play essential roles in defending against persistent microbes, including mycobacteria (such as those that cause tuberculosis, leprosy and other hard-hitting infections).7 By activating SIRT3, pure honokiol is shown to offer critical protective benefits related to aging, immune health, cardiovascular function and more.
Potent Antiviral Activity
Honokiol exhibits potent antimicrobial activity, including antiviral actions against a number of dangerous infections. One study showed that pure honokiol significantly inhibited infection by Dengue virus type 2, by blocking viral replication, suppressing viral gene expression and inhibiting cytotoxic effects.8
Protects the Respiratory System
Honokiol demonstrates an affinity for lung tissue, and is shown to reduce symptoms of asthma9 and support the treatment of pulmonary fibrosis.10 Another study using magnolia bark extract containing honokiol, showed protection against pneumonia during influenza infection.11
Broad Spectrum, Synergistic Benefits
In addition to these benefits, pure honokiol is also a potent neuroprotector, capable of crossing the blood-brain barrier to exert a range of actions against neuroinflammation and neurodegeneration—which researchers are also investigating as additional complications of COVID-19.
Pure honokiol also demonstrates synergy with other therapies, including synergy modified citrus pectin in reducing inflammation, favorably modulating transcription factors related to immunity and increasing antioxidant status.12
Fundamental Support for Acute and Long-term Health
With powerful beneficial mechanisms, including broad-spectrum immune modulation and support, cellular and gene expression and others, these evidence-based nutraceutical agents are earning recognition as multifaceted adjuncts to support key processes for optimal long-term health—starting with the most fundamental: immune modulation and support.
1 Laura Díaz-Alvarez and Enrique Ortega. The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens. Mediators of Inflammation. 2017(8):1-10.
2 Caniglia JL, Guda MR, Asuthkar S, Tsung AJ, Velpula KK. A potential role for Galectin-3 inhibitors in the treatment of COVID-19. PeerJ. 2020;8:e9392. Published 2020 Jun 15. doi:10.7717/peerj.9392
3 Xu, G. R., Zhang, C., Yang H. X., Sun J. H., Zhang Y., Yao T. T., Li Y., Ruan L., An R., Li A. Y. (2020) Modified citrus pectin ameliorates myocardial fibrosis and inflammation via suppressing galectin-3 and TLR4/MyD88/NF-κB signaling pathway. Biomed Pharmacother Mar 11; 126:110071. doi: 10.1016/j.biopha.2020.110071.
4 Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5.
5 Fogarty H, Townsend L, Ni Cheallaigh C, et al. COVID19 coagulopathy in Caucasian patients [published online ahead of print, 2020 Apr 24]. Br J Haematol. 2020;10.1111/bjh.16749. doi:10.1111/bjh.16749.
6 Lee, S.-Y., & Cho, J.-Y. Inhibitory effects of honokiol on LPS and PMA-induced cellular responses of macrophages and monocytes. BMB Reports. 2009;42(9), 574–579.
7 Kim TS, et al. SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions. Autophagy. 2019 Aug;15(8):1356-1375.
8 Fang, Chih Yeu et al. Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection. Viruses 7.9 (2015): 4894–4910.
9 Hong T, et al. Oral administration of honokiol attenuates airway inflammation in asthmatic mouse model. Pak J Pharm Sci. 2018 Jul;31(4):1279-1284.
10 Pulivendala G, et al. Honokiol: A polyphenol neolignan ameliorates pulmonary fibrosis by inhibiting TGF-β/Smad signaling, matrix proteins and IL-6/CD44/STAT3 axis both in vitro and in vivo. Toxicol Appl Pharmacol. 2020 Mar 15;391:114913.
11 Wu XN, et al. Protective effect of a polyphenolic rich extract from Magnolia officinalis bark on influenza virus-induced pneumonia in mice. J Ethnopharmacol. 2011 Mar 8;134(1):191-4.
12 Ramachandran C, et al. Synergistic Antioxidant and Anti-Inflammatory Effects between Modified Citrus Pectin and Honokiol. Evid Based Complement Alternat Med. 2017;2017:8379843.
Dr. Isaac Eliaz is a recognized expert in the field of integrative medicine since the early 1980s, with a specific focus on cancer, immune health, detoxification and mind-body medicine. He is a respected formulator, clinician, researcher, author and educator. As part of his commitment to the advancement of integrative medicine, Dr. Eliaz partners with leading research institutes and has co-authored numerous peer-reviewed papers on innovative therapies for immune enhancement, heavy metal toxicity, and cancer prevention and treatment. He is founder and medical director of Amitabha Medical Clinic and Healing Center in Santa Rosa, CA, where he and his team of practitioners pioneer individualized treatments for cancer and chronic illness.