Hydrogen water, Hydrogen inhalation, H2 IV, H2 saline, H2 bath.

Anti- aging, anti- oxidant, anti-apoptosis, cytokine protection, anti- inflammatory, reduces ROS, neutralize hydroxyl radicals, and make us free from oxidative stress.

H2 directly increases the permeability of Oxygen and strengthen blood and nerves. It naturally detoxifies human body from the acidic and toxic presence.

H2 used by cancer patients to free from acute oxidative stress, pain, skin damage, hair loss and to prevent spreading.

H2 used by Diabetes patients to regulate insulin secretion, regulate carbohydrate – lipid metabolism and chronic hyperglycemia.

H2 used by cardiovascular patients- inhalation of H2 improves cardio metabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation induced injury, obesity and diabetes in clinical trials.

H2 used by Kidney patients on renal calculi, fibrosis and drug induced nephrotoxicity. H2 is biologically active as an anti-inflammatory ad antioxidant. Thus, studies indicate that H2 therapy along with hemodialysis has a better treatment outcome. Iron-induced oxidative stress has been found to be a central player in the pathogenesis of kidney injury. Recent studies have indicated H2 can be used as a novel antioxidant to protect cells. Renal injury, apoptosis and oxidative stress induced by chronic intermittent hypoxia (CIH) were strikingly attenuated in H2 treatment.

The incidence of chronic graft‐versus‐host disease (cGVHD) is rising in recent years, which has been the leading cause of non‐transplantation mortality post allogeneic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti‐inflammatory, antioxidant, anti-fibrosis effects. Therefore, molecular hydrogen has therapeutic effects on cGVHD. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD.

H2 for Covid-19 treatment. H2 has a miracle effect on prevention of cytokine stome and anti- inflammatory. H2 protects aveola from pulmonary fibrosis, hypoxia, hypoxemia and edema. H2 increases oxygen permeability and works as anti-apoptisis. Hydrogen as an anti-oxidant easily penetrates to cell and easily do cell repair. H2 administration gives 10 times faster result than O2 administration.

The exact molecular mechanisms of the effects of low-dose H2 remain unclear. H2 can modulate signal transduction across multiple pathways, but its primary molecular targets have not been determined. Examining critical overlapping signaling molecules would help map crosstalk among critical pathways. To fully explain the biological functions of H2 , its molecular mechanisms of action must be clarified.

The role of H2 as an antioxidant has garnered the most attention among many proposed biological activities. H2 is a specific scavenger of •OH and ONOO-, which are very strong oxidants that react indiscriminately with nucleic acids, lipids, and proteins, resulting in DNA fragmentation, lipid peroxidation, and protein inactivation.

H2 administration decreases expression of various oxidative stress markers, such as myeloperoxidase, malondialdehyde, 8-hydroxy-desoxyguanosine8-OHdG, 8-iso-prostaglandin F2a, and thiobarbituric acid reactive substances in all human diseases and rodent models.

In 2016, researchers proposed that H2 could decrease ROS content in Ganoderma lucidum depending on the presence of endogenous glutathione peroxidase.

Anti-inflammation

A 2001 study found that breathing high-pressure H2 could cure parasite-induced liver inflammation, and was the first demonstration of the anti-inflammatory properties of H2. H2 has exhibited anti-inflammatory activities in various injury models. Typically, H2 inhibits oxidative stress-induced inflammatory tissue injury via down regulation of pro-inflammatory and inflammatory cytokines, such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α(TNF-α), intercellular cell adhesion molecule-1 , high-mobility group box 1(HMGB-1), nuclear factor kappa B (NF-κB), and prostaglandin E2. H2 improved survival rate and reduced organ damage in septic mice by down regulating early and late pro-inflammatory cytokines in serum and tissues, suggesting the potential use of H2 as a therapeutic agent for conditions associated with inflammationrelated sepsis/multiple organ dysfunction syndrome. Additionally, H2 released from intestinal bacteria has been suggested to suppress inflammation.

Anti-apoptosis

H2 exerts anti-apoptotic effects by up- or down regulating apoptosis-related factors. ]. H2 further inhibits apoptosis by regulating signal transduction within and between specific pathways. Hong, et al. first confirmed in 2014 that the H2 -triggered neuroprotective effect is at least partially associated with anti-apoptotic protein kinase B pathway (also known as the Akt/glycogen synthase kinase 3β(GSK3β) pathway)activation in neurons.

Gene expression alterations

H2 administration induces expression of diverse genes, including NF-κB , c-Jun N-terminal kinase (JNK) , proliferation cell nuclear antigen, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP) , and creatine kinase . Some of these molecules may be secondarily regulated by H2 , and some may be direct H2 targets. In the normal rat liver, H2 was found to have little effect on the expression of individual genes, but gene ontology analysis demonstrated upregulation of oxidoreduction-related genes .The anti-inflammatory and anti-apoptotic properties of H2 could be realized by modulating expression of proinflammatory and inflammatory cytokines, and apoptosisrelated factors.

H2 as a gaseous signal modulator

Oxidative stress impacts multiple signaling pathways, including the extracellular signal-regulated protein kinase (ERK)1/2, NF-κB, JNK, andnuclear factor-erythroid 2p-related factor 2 (Nrf2) pathways. Along with selectively scavenging •OH, H2 may alleviate oxidative stress-induced injury by targeting these pathways. Additional studies confirmed that H2 could exert anti-inflammatory effects by regulating Toll -like receptor 4 (TLR4) signaling , and anti-apoptotic effects through Ras-ERK1/2-MEK1/2 and Akt pathway inactivation.H2 may also protect against allergic reactions by directly modulating FcεRI-related signaling, rather than through radical-scavenging activity.

H2 biological effects and possible mechanisms of action. (A) H2 has selective anti-oxidative, anti-inflammatory and anti-apoptotic properties. Exogenous damage due to such factors as radiation induces excess cellular ROS production. H2 penetrates biomembranes and effectively reaches cell nuclei. H2 selectively scavenges •OH and ONOO- and thus prevents DNA damage. H2 also downregulates the expression of pro-inflammatory and inflammatory cytokines, such as IL-1β, IL-6, TNF-α, ICAM-1, and HMGB-1, and of pro-apoptotic factors, such as caspase-3, caspase-12, caspase-8 and Bax. H2 upregulates the expression of anti-apoptotic factors, such as Bcl-2 and Bcl-xL.

Oral intake of hydrogen-rich water

While inhalation of H2 produces rapid effects, this delivery method may not be practical for daily preventive therapy. Due to safety concerns, H2 concentrations and dosages must be strictly controlled. Unlike gaseous H2 , solubilized H2 [H2 -dissolved water or hydrogen-rich water (HW)] is portable, safe, and easily administered . H2 can be dissolved in water up to 0.8 mM (1.6 mg/L) under atmospheric pressure at room temperature without changing pH, and 0.8 mM HW effectively improved obesity in mice model . Additionally, H2 accumulation in the liver after oral HW administration can be measured with a needle-type hydrogen electrode to determine whether consumption of small amounts of H2 over a short time period can efficiently improve various disease models. In vitro experiments demonstrated that carbohydrate polymers, including glycogen and starch, have an affinity for H2 , and some studies found that drinking HW produced beneficial effects in disease models, such as Parkinson’s disease, oral palatal wound , radiation-induced oxidative injuries , periodontal tissue aging, and depressive-like behavior.

Injection of hydrogen-rich saline

Although administering oral HW is safe and convenient, controlling the concentration of H2 administered can be difficult, as it evaporates in water over time and can be lost before absorption in the gastrointestinal tract. Thus, hydrogen-rich saline (HS) injections may deliver more accurate H2 doses . Experimental evidence suggests that HS could be successfully administered by peritoneal or intravenous injection. Injection of hydrogen-rich saline Although administering oral HW is safe and convenient, controlling the concentration of H2 administered can be difficult, as it evaporates in water over time and can be lost before absorption in the gastrointestinal tract. Thus, hydrogen-rich saline (HS) injections may deliver more accurate H2 doses. Experimental evidence suggests that HS could be successfully administered by peritoneal or intravenous injection. For example, HS injection had neuroprotective effects in a spinal cord injury rat model.

Direct diffusion of hydrogen

Baths, eye drops, and immersion Because H2 can easily penetrate the skin and be distributed via blood flow throughout the body, a warm HW bath can be used therapeutically in daily life. Warm HW baths may minimize UVA-induced skin damage . A cold storage device equipped with a HW bath may be cytoprotective in various diseases and in organ transplantation. H2 dissolved in saline has also been used to directly treat the ocular surface. Antioxidant therapy via an H2 -enriched irrigation solution has been suggested as a new potent corneal treatment to prevent blindness caused by alkali burn.

Increased intestinal hydrogen

H2 is spontaneously produced in the body through fermentation of undigested carbohydrates by resident enterobacterial flora. Escherichia coli can produce a considerable amount of H2 through the hydrogenase enzyme. However, few groups have studied the physiological and therapeutic functions of H2 derived from the gastrointestinal tract. H2 produced by bacterial fermentation in the gut shortens colonic transit, and this effect was more prominent in the proximal than the distal colon.

• Rapid action, straightforward delivery does not influence blood physiological parameters (temperature, blood pressure, pH, pO2 ).
• Suitable to defense against acute oxidative stress.

• Dissolving H2 in water up to 0.8 mM under atmospheric pressure at room temperature.
• Convenient, easily administered, safe, efficient.
• Easily evaporates and is lost in the stomach or intestine.
• Difficult to control H2 concentration administered.

Delivery of more accurate H2 concentrations.

• Bath, Eye drops, Spray on plants or immerse plants.
• 1. Low cost. Cold storage of transplanted organs.
• 2. Convenient and safe.
• H2 is considered as the natural medicine of 21st century.