INTRODUCTION:

L-methionine is an essential sulfur-containing amino acid crucial for human nutrition¹. Thus, s-methylmethionine sulfonium chloride (MMSC) (C₆H₁₄NO₂S•Cl) is a derivative of methionine and is classified as a vitamin-like substance². It has been referred to as vitamin U due to its effectiveness in the prevention and treatment of gastrointestinal ulcers³, although this designation is not widely accepted in the scientific community. This compound has been used in therapy since ancient times, notably by Hippocrates⁴.

MMSC is generally considered safe when consumed through whole foods. However, there is limited information regarding its safety and potential side effects when taken as a dietary supplement. The European Chemicals Agency has warned that MMSC can cause irritation to the eyes, skin, or respiratory system upon direct contact⁵. MMSC is a hydrophilic compound characterized by its functional properties and cationic structure, which includes an α-amino acid terminal group (refer to figure 1)⁶.

Figure 1. Chemical Structure of Vitamin U

According to the methodological guidelines MP 2.3.1.0253-21, adequate intake level for adults is 200 mg/day⁷. MMSC is predominantly present in plant-based foods⁸, particularly in green leafy vegetables, asparagus, carrots, tomatoes and cabbage. MMSC, obtained by biotechnological or chemical synthesis, is also used for the needs of the pharmaceutical and food industries^8,9.

The presence of a functional sulfonium group positions MMSC as a crucial intermediate in various metabolic pathways within the human body. The biosynthesis of this compound involves a multi-step process starting from L-methionine, which is converted to s-adenosylmethionine and then modified by methionine-S-methyltransferase to produce s-adenosylhomocysteine^4,10. MMSC is characterized as an activated form of methionine that can effectively participate in methylation without inhibiting the process, making it a valuable component in various biochemical reactions. In contrast, S-adenosylmethionine, which is a naturally-occurring compound found in almost every tissue and fluid in the body, acts as an inhibitor of a key enzyme in this metabolic system, which is responsible for the conversion of one-carbon compounds into methyl radicals, specifically by converting the methylene group of folate into methyl. It is also involved in many important processes. S-adenosylmethionine plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals, such as serotonin, melatonin, and dopamine.

Gastroprotective Effect:

For over a century, peptic ulcer disease has significantly contributed to both morbidity and mortality rates¹¹. Despite modern treatment standards for patients with gastroenterological conditions not including the use of MMSC, the history of its effectiveness in this patient group is particularly noteworthy. In 1949, a study involving 13 patients diagnosed with peptic ulcers was conducted, wherein they were administered fresh cabbage juice¹². The results demonstrated a rapid healing of the peptic ulcers, as evidenced by radiological and gastroscopic evaluations. These findings suggest that dietary factors, particularly those associated with the consumption of fresh cabbage juice, may significantly contribute to the pathogenesis of peptic ulcers in humans.

In a 2007 study, the effects of MMSC at a dosage of 200 mg/kg on pigs were assessed over 49 days, focusing on nutritional performance and the prevention or treatment of oesophagogastric ulcers¹³. The results showed no significant differences in weight gain, feed intake, or backfat measurements among different groups of pigs. The compound did not prevent the progression of ulcers in pigs with initially low ulcer scores, nor did it show significant effects on those with high pre-existing ulcer scores. However, a detailed analysis indicated that there were statistically significant reductions in ulcer scores among the high ulcer group compared to other groups throughout the experiment. Another study investigated the effects of a combined treatment of MMSC at a dose of 500mg/kg and famotidine (a highly selective histamine H₂-receptor antagonist¹⁴) at a dose of 3 mg/kg administered orally via gavage, with famotidine given 30 minutes before MMSC once daily for 7 days¹⁵. The findings of this study suggest that the combination therapy promotes the biosynthesis and accumulation of mucin, which may counteract the inhibitory effects of famotidine on the functionality of gastric mucosal cells. This indicates that the integrated pharmacological approach could enhance the efficacy of treatment strategies of gastric ulcers.

A 2023 clinical trial by Drozdov V.N. assessed the impact of 300 mg daily MMSC supplementation over 6 months on dyspeptic symptoms and quality of life in 37 patients with chronic gastritis¹⁶. Using the Gastrointestinal Symptom Rating Scale (GSRS) for evaluation at baseline, 3 months, and 6 months, the study found that MMSC significantly alleviated dyspeptic symptoms and improved patients' quality of life.

Hepatoprotective Effect:

Sokmen and others investigated the hepatoprotective effects of MMSC in a rat model of liver injury induced by valproic acid, administered at 500 mg/kg/day for 15 days¹⁷. Valproic acid is a high risk hepatotoxicity anticonvulsant¹⁸. MMSC was given concurrently at 50 mg/kg/day. The administration of MMSC resulted in a significant reduction in the elevated levels of aspartate and alanine transaminases (ALS, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), myeloperoxidase (MPO), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), and xanthine oxidase (XO), as well as a decrease in lipid peroxidation levels (LP). Conversely, there was a marked increase in paraoxonase activity (PON) and glutathione levels (GSH) following the administration of MMSC. These findings suggest that MMSC may be an effective therapeutic option to alleviate valproic acid-induced hepatotoxicity, likely by reducing oxidative stress.

Abouzed evaluated the protective effects of MMSC against liver damage induced by D-galactose in rats¹⁹. Chronic systemic administration of D-galactose via subcutaneous or ip routes induces oxidative damage by activating nitric oxide synthase²⁰. The rats received D-galactose i.p. at a dosage of 50mg/kg daily for 8 weeks, alongside MMSC at the same dosage. MMSC was found to be a promising therapeutic agent that aids in weight maintenance, lipid profile regulation, blood glucose control, and the balance of oxidant and antioxidant enzymes, as well as improving various health parameters like HbA1c, ALT, AST, GGT, albumin, and fructosamine.

Antitumor Activity:

A substantial body of research has documented the anti-inflammatory, antioxidant, and antitumor effects of MMSC²¹, with a particular focus on its relevance to hepatocellular carcinoma²². In a study involving male Wistar albino rats, hepatocellular carcinoma was induced through the administration of diethyl nitrosamine at a dosage of 200mg/kg and carbon tetrachloride at 1mL/kg. MMSC was administered at a dosage of 50mg/kg per day via a gastric tube for a period of 16weeks. This treatment resulted in notable enhancements in liver function biomarkers, including AST, GGT, albumin, globulin, albumin/globulin ratio. MMSC treatment was associated with a decrease in the expression levels of inflammatory and tumor-related markers, such as tumor necrosis factor-alpha (TNF-α), induced nitric oxide synthase (iNOS), transforming growth factor (TGF-1β), and glypican 3 (GP3). The histopathological alterations in liver tissue linked to hepatocellular carcinoma showed improvement subsequent to MMSC administration.

Nephroprotective Effect:

Nephrotoxicity is the most prevalent renal complication, arising from the body's exposure to pharmaceuticals or toxic substances²³. The impact of MMSC on oxidative stress, inflammation, and fibrosis in the context of renal damage induced by valproic acid (500mg/kg/day, i.p.) was investigated using female Sprague Dawley rats²⁴. MMSC was administered at 50mg/kg/day prior to valproic acid treatment for 15 days. Results showed that MMSC significantly reduced histopathological changes and improved Na(+)/K(+)-ATPase activity, indicating renal protection. It also exhibited antioxidant properties by lowering malondialdehyde levels (MDA) and xanthine oxidase levels (XO) while increasing glutathione, catalase, and superoxide dismutase activities (SOD). Additionally, MMSC demonstrated anti-inflammatory effects by decreasing TNF-α, interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) levels, as well as reducing adenosine deaminase activity. Its anti-fibrotic effects were evidenced by lower levels of TGF-β, collagen-1, and arginase activity. Overall, MMSC shows potential as a protective agent against renal damage linked to valproic acid therapy.

Wound healing and photoprotective effects:

Skin wounds exhibit some histopathological characteristics similar to those of gastric ulcers, suggesting that MMSC may enhance the healing of skin wounds. Various concentrations of MMSC were prepared (1%, 5%, and 10% w/w) in pure vaseline and applied topically to excisional and chemical wounds in rats²⁵. Results showed that MMSC significantly improved wound closure and re-epithelialization compared to the control group. Additionally, MMSC stimulated the proliferation and migration of human dermal fibroblasts, crucial for skin healing, through the activation of the ERK1/2 signaling pathway. Inhibiting ERK activity reduced fibroblast proliferation and migration, reinforcing the conclusion that MMSC promotes skin repair by activating dermal fibroblasts, highlighting its potential as an effective treatment for skin wounds¹⁸. Kim WS and his team investigated the photoprotective effects of MMSC against ultraviolet B (UVB) exposure, known for its negative effects on the immune and other systems²⁶, both in vitro and in vivo²⁷. Their studies revealed that MMSC, administered at concentrations of 5% and 10% before and after UVB exposure, improved the survival of keratinocyte progenitor cells and human dermal fibroblasts, while reducing UVB-induced apoptosis. MMSC decreased reactive oxygen species production, enhanced collagen synthesis, and lowered matrix metalloproteinase-1 expression in fibroblasts exposed to UVB. These findings suggest that MMSC could be a valuable cosmetic ingredient for skin protection against UVB radiation.

Two other derivatives of MMSC were shown to increase human dermal fibroblasts and immortalized human keratinocyte cell line proliferation, improve their survival by protecting against ultraviolet exposure, suggesting their usefulness as cosmetic raw materials²⁸.

Hypolipidemic effect:

A study investigating the impact of MMSC on aminonucleoside-induced nephrotic hyperlipidemia in experimental animals revealed that a regimen of oral MMSC administration (at a dosage of 1000mg/kg of body weight daily) resulted in a reduction of cholesterol and phospholipid levels in the blood plasma²⁹. The experiment demonstrated a notable trend towards the amelioration of nephrotic syndrome in the subjects, characterized by a decrease in proteinuria and an increase in urine output. The findings from this study suggest potential therapeutic applications of MMSC in the management of nephrotic syndrome and its associated hyperlipidemia. An in vitro investigation using the 3T3-L1 pre-adipocyte cell line demonstrated that introducing varying concentrations of MMSC (10 to 100mM) into fat differentiation-inducing media led to a significant reduction in triglyceride levels and the expression of key adipogenic factors such as C/EBP-α, PPAR-γ, adipsin, ADD-1, and glycerol-3-phosphate dehydrogenase (GPDH) activity³⁰. Additionally, higher MMSC concentrations resulted in increased AMP-activated protein kinase (AMPK) activity. However, changes in Bcl-2 and Bax levels were not statistically significant. These results indicate that MMSC may inhibit adipocyte differentiation by down-regulating adipogenic factors and up-regulating AMPK activity.

Crystalline lens protective effect:

An experimental study on Sprague Dawley rats demonstrated that MMSC may reduce lens damage caused by valproic acid³¹. The rats were given valproic acid at a dose of 500mg/kg/day for 15 days, alongside MMSC at 50mg/kg/day. On the sixteenth day, biochemical assessments revealed significant lens damage in the valproic acid group, characterized by increased lipid peroxidation and elevated activities of aldose reductase and sorbitol dehydrogenase, while levels of glutathione and activities of several antioxidant enzymes were reduced. The group receiving MMSC showed a reversal of these toxic effects, suggesting that MMSC's antioxidant properties can protect against lens damage induced by valproic acid.

Brain tissues protective effect:

A recent investigation examined the neuroprotective effects of MMSC in the context of galactosamine-induced hepatotoxicity in female Sprague-Dawley rats³². The subjects received MMSC at a dosage of 50 mg/kg/day via gavage for a duration of 3 days, followed by a single intraperitoneal injection of galactosamine (500mg/kg) administered one hour after the final MMSC treatment. The findings revealed that galactosamine administration resulted in elevated levels of lipid peroxidation, hydroxyproline, and nitric oxide, alongside a reduction in Na+/K+-ATPase activity. Conversely, the administration of MMSC mitigated these adverse effects, thereby underscoring its protective role against brain damage induced by galactosamine. Turkyilmaz studied the protective effects of MMSC against brain damage induced by amiodarone, characterized by neurotoxicity risk in high doses³³, in male Sprague-Dawley rats³⁴. The rats received MMSC at a dosage of 50mg/kg/day for 7 days, followed by a single dose of 100mg/kg of amiodarone. MMSC administration led to increased levels of brain glutathione and total antioxidants, as well as enhanced activities of various enzymes including catalase and superoxide dismutase. MMSC treatment also resulted in decreased levels of lipid peroxidation, protein carbonyls, total oxidant status, oxidative stress index, reactive oxygen species, and activities of myeloperoxidase, acetylcholine esterase, and lactate dehydrogenase. Therefore, the administration of MMSC underscoring its protective role against brain damage induced by amiodarone.

A recent study investigated the protective effects of MMSC on gingival tissue using male Sprague-Dawley rats³⁵. The study involved administering MMSC at 50 mg/kg/day for 7 days, followed by a single dose of 100 mg/kg amiodarone one hour before the MMSC treatment. MMSC significantly increased lipid peroxidation and sialic acid levels, while also enhancing glutathione levels and superoxide dismutase activity, what could possibly be used in the treatment of gingivitis³⁶.

Table 1. Pleiotropic effect of s-methylmethionine sulfonium chloride

Effect	Ref.	MMSC dose	Model	Results
Gastroprotective	Cheney G.¹²	unidentified (cabbage juice) orally	clinical (13 patients)	a rapid healing of the peptic ulcers
	Kopinski J.¹³	200mg/kg, 49 days, orally	pigs	↓ in scores among the high ulcer group
	Ichikawa T¹⁵	500mg/kg, 7 days orally, famotidine combination	rats	↑ of mucin biosynthesis and accumulation
	Drozdov V.N¹⁶	300mg/day, 6-month, orally	clinical (37 participants)	↓ (significant) the severity of dyspeptic symptoms and improved the quality of life
Hepatoprotective	Sokmen BB¹⁷	50mg/kg/day, 15 days, orally	rats, valproic acid-induced hepatotoxicity	↓ (significant): ALS, AST, ALP, LDH, MPO, SDH, GDH, XO, LP; ↑: PON, GSH
Hepatoprotective	Abouzed TK¹⁹	50mg/kg/day, 8-week, orally	rats, D-galactose- induced hepatotoxicity	↓ oxidative stress and hepatic damage, ↑ HbA1c, ALT, AST, GGT, albumin, fructosamine
Antitumor	Abouzed TK²¹	50mg/kg/day, 16 weeks, orally	rats, diethyl nitrosamine/ carbon tetrachloride- hepatocarcinoma	↑ (significant) AST, GGT, albumin, globulin, albumin/globulin ratio; ↓ expression TNF-α, iNOS, TGF-1β, GP3
Nephroprotective	Gezginci-Oktayoglu S²⁴	50 mg/kg/day, 15 days, orally	rats, valproic acid-induced renal toxicity	↓ histopathological alterations, alongside ↑ Na⁺/K⁺-ATPase activity; ↓ MDA, XO; ↑ GSH, SOD, catalase activity; ↓ TNF-α, IL-1β, MCP-1, ADA; TGF-β, collagen-1, arginase activity
Wound healing	Kim WS²⁵	1%, 5%, and 10% w/w in pure vaseline	rats, excisional and chemical wound generation	↑ wound closure, re-epithelialization; ↑ the proliferation, migration of human dermal fibroblasts; ↑ of ERK1/2 signaling pathway
Photoprotective	Kim WS²⁷	5% and 10%	in vitro	↓ reactive oxygen species; ↑ collagen synthesis; ↓ the expression of matrix metalloproteinase-1
Photoprotective	Kim WS²⁷	5% and 10%, topical	rats	↓ (significant) the UV B-induced erythema index and the depletion of Langerhans cells
Hypolipidemic	Seri K²⁹	1000mg/kg, oraly, daily	rats, aminonucleoside-induced nephrotic hyperlipidemia	↓cholesterol, phospholipid levels; ↓ (a notable trend) of nephrotic syndrome
Hypolipidemic	Lee NY³⁰	10, 50, 70, 90, and 100 mM	in vitro, pre-adipocyte cell line 3T3-L1, cultured to overconfluency	↓ TGs, ↑ adipogenic factors: C/EBP-α, PPAR-γ, adipsin, ADD-1, GPDH activity; ↑ AMPK activity
Lens protective	Tunali S³¹	50mg/kg/day, 15 days, orally	rats, valproic acid-induced lens injury	↓ LP, AR, SDH; ↑ GSH, SOD, GPx, GR, GSTs, PON
Brain tissues protective	Bayrak BB³²	50mg/kg/day, 3 days, orally	rats, galactosamine-induced hepatotoxicity	↓ LP, NO and hydroxyproline; ↑ Na⁺/K⁺-ATPase

Note: notation is used ↓ – reduction, decline, decrease, ↑ – improve, increase, enhanceme, stimulate,

Technological developments of s-methylmethionine sulfonium chloride:

MMSC is primarily found in dietary supplements rather than the pharmaceutical market, with limited comprehensive data on its use globally. In Russia, a registered dietary supplement containing 300mg of MMSC claims to protect the stomach and duodenum mucosal lining, normalize gastric acidity, improve secretory functions, regulate gastrointestinal motility, stimulate cellular recovery, alleviate discomfort, and enhance liver metabolism³⁷. A 2023 study explored a pharmaceutical formulation of microencapsulated MMSC extracted from Brassica oleracea L. var. capitata (cabbage) for treating peptic ulcers, utilizing various extraction techniques and microencapsulation methods. The study confirmed the successful encapsulation and release of MMSC through morphological analysis. Results showed that the microcapsules exhibited a uniform, spherical structure, and HPLC confirmed the presence of the desired compounds. FTIR showed successful interactions between the shell materials and the encapsulated extract. In vitro release studies indicated effective release profiles in simulated gastric and intestinal fluids, achieving a maximum encapsulation efficiency of 86.92% and a release rate of 93.6% for microcapsules made with gum Arabic³⁸.

CONCLUSIONS:

Notably, the anti-ulcer properties, which inspired the designation of MMSC as vitamin U, emerge as the most intriguing attributes and have garnered significant attention from researchers in the field. Experimental and clinical evidence substantiates the gastroprotective properties of MMSC, suggesting its potential application in combination pharmacotherapy for peptic ulcer disease to enhance therapeutic efficacy and to mitigate exacerbations of chronic gastrointestinal mucosal disorders. The mechanism of action of MMSC is associated with its role as a metabolic agent, which specifically influences various metabolic processes. Its biological roles are not well understood. Speculated roles include methionine storage, use as a methyl donor, regulation of S-adenosylmethionine. This interaction accounts for the diverse pharmacodynamic effects observed and, consequently, the potential applications in clinical practice⁶. Furthermore, existing literature indicates that MMSC exhibits antioxidant, hypolipidemic, and anti-inflammatory effects. Notably, from a scientific perspective, the capacity of MMSC to avert drug-induced damage to the liver and kidneys, as well as its potential to prevent drug-induced lens injury, warrants particular attention, which in the future may serve as a basis for expanding the list of indications for the use of vitamin U in clinical practice.

REFERENCES:

1. Subhadeep G, Kunja BS, Ajit KB. Induced Mutation, Development of Multiple Analogue Resistant Strain and Protoplast Fusion for L-Methionine Fermentation by Corynebacterium glutamicum. Res. J. Pharm. Dosage Form. and Tech. 2014; 6(1): 01-06.

2. Kim WS, et al. Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure. Biomol. Ther. 2018; 26: 306–312.

3. Kopinski J, Fogarty R, McVeigh J. Effect of s-methylmethionine sulphonium chloride on oesophagogastric ulcers in pigs. Aust. Veter. J. 2007; 85: 362–367.

4. Patel AD and Prajapati NK. Review on Biochemical Importance of Vitamin-U. Journal of Chemical and Pharmaceutical Research. 2012; 4(1): 209-215.

5. European Chemicals Agency s-methylmethionine [online]. Available from: http://echa.europa.eu (Last accessed 01.12.2024).

6. Kim KT, et al. Effect of enhancers on in vitro and in vivo skin permeation and deposition of S-methyl-l-methionine. Biomol. Ther. 2017; 25(4): 434-440. Doi: 10.4062/biomolther.2016.254.

7. Methodological recommendations MP 2.3.1.0253-21 "Norms of physiological needs for energy and nutrients for various population groups of the Russian Federation" [in Russian] [online]. Available from: https://www.garant.ru/products/ipo/prime/doc/402716140/. (Last accessed 25.12.2024)

8. Gun-Hee Kim. Determination of vitamin U in food plants. Food Sci. Technol. Res. 2003; 9(4): 316-319.

9. Viktorovna KT, et al. S-methylmethionine (vitamin U): experimental studies and clinical perspectives [in Russian]. Voprosy pitaniya. 2018; 87(5): 70-76. Doi: 10.24411/0042-8833-2018-10055.

10. Sauter M, et al. Methionine salvage and S-adenosylmethionine: essential links between sulfur, ethylene and polyamine biosynthesis. The Biochemical journal. 2013; 451(2): 145-54 .

11. Mahurkar N, ul hasan SMS. Synergistic Antiulcer Effect of Melatonin and Esomeprazole Combination in Pylorus Ligation, Ethanol, Aspirin induced Peptic Ulcers. Asian J. Pharm. Res. 2015; 5(1): 10-14. Doi: 10.5958/2231-5691.2015.00002.7

12. Cheney G. Rapid healing of peptic ulcers in patients receiving fresh cabbage juice. Calif Med. 1949; 70(1): 10-5.

13. Kopinski J, Fogarty R, McVeigh J. Effect of s-methylmethionine sulphonium chloride on oesophagogastric ulcers in pigs. Australian Vet. J. 2007; 85: 362-367.

14. Pooja K, et al. Validated Analytical Method for Multicomponent Analysis of Famotidine and Ofloxacin in Bulk drug and Tablet Formulation by using UV-Visible Spectrophotometer and RP-HPLC. Asian Journal of Pharmaceutical Analysis. 2023; 13(3): 162-0. Doi: 10.52711/2231-5675.2023.00026

15. Ichikawa T, et al. Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucosa. J Gastroenterol Hepatol. 2009; 24(3): 488-92. Doi: 10.1111/j.1440-1746.2008.05667.x.

16. Drozdov VN, et al. Effect of 6-month S-methylmethionine intake on the quality of life and dyspepsia symptoms in patients with chronic gastritis [in Russian]. Voprosy Pitaniya. 2023; 92(2): 80-86. DOI: 10.33029/0042-8833-2023-92-2-80-86

17. Sokmen BB, Tunali S, Yanardag R. Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats. Food Chem Toxicol. 2012; 50(10): 3562-3566. Doi: 10.1016/j.fct.2012.07.056.

18. Vanitha K, Desu PK. Formulation Development and Evaluation of Sodium Valproate and Valproic acid Extended Release Tablets. Res. J. Pharma. Dosage Forms and Tech. 2019; 11(2): 74-80. Doi: 10.5958/0975-4377.2019.00012.0

19. Abouzed TK, et al. The Attenuative Effects of Zinc Oxide Nanoparticles and S-Methylmethionine Sulfonium Chloride Against D-Galactose Induced Liver Oxidative Stress and Apoptosis in Albino Rats. Pakistan J. Zool. 2024; 1-10. Doi: 10.17582/journal.pjz/20230523160530

20. Sriram BS, et al. An Experimental Study Evaluating the dose of oral D-Galactose on aging Induction in wistar albino male Rats. Research J. Pharm. and Tech. 2020; 13(7): 3289-3292. Doi: 10.5958/0974-360X.2020.00583.1

21. Abouzed TK, et al. Antitumor and Antioxidant Activity of S-Methyl Methionine Sulfonium Chloride against Liver Cancer Induced in Wistar Albino Rats by Diethyl Nitrosamine and Carbon Tertrachloride. International Journal of Environmental Research and Public Health. 2021; 18(18): 9726. Doi: 10.3390/ijerph18189726

22. Dhandhukiya MK, Saiyed MS. Hepatocellular Carcinoma: A Review. Asian Journal of Research in Pharmaceutical Sciences. 2023; 13(2): 171-179. Doi: 10.52711/2231-5659.2023.00030

23. Chaurasia S, Yadav S, Chandrika PM. Nephroprotective effects of Hydroalcoholic Extracts of Four selected Indian Medicinal Plants in Gentamicin-induced Nephrotoxic Wistar Rats. Research Journal of Pharmacy and Technology. 2023; 16(9): 4307-3. Doi: 10.52711/0974-360X.2023.00705

24. Gezginci-Oktayoglu S, et al. Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties. Protoplasma. 2016; 253(1): 127-135. Doi: 10.1007/s00709-015-0796-3.

25. Kim WS, et al. Accelerated wound healing by S-methylmethionine sulfonium: evidence of dermal fibroblast activation via the ERK1/2 pathway. Pharmacology. 2010; 85(2): 68-76. Doi: 10.1159/000276495.

26. Diah D, Chiquita P, Retno PR. Effects of Different Doses of Systemic UVB 310nm Irradiation in Gingivitis Rat Model. Research Journal of Pharmacy and Technology. 2024; 17(11): 5317-4. Doi: 10.52711/0974-360X.2024.00814

27. Kim W-S, et al. The Photoprotective Effect of S-Methylmethionine Sulfonium in Skin. International Journal of Molecular Sciences. 2015; 16(8): 17088-17100. Doi: 10.3390/ijms160817088

28. Kim WS, et al. Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure. Biomol Ther (Seoul). 2018; 1; 26(3): 306-312. Doi: 10.4062/biomolther.2017.109.

29. Seri K, et al. Effects of S-methylmethionine (vitamin U) on experimental nephrotic hyperlipidemia. Arzneimittelforschung. 1979; 29(10): 1517-1520.

30. Lee NY, et al. Inhibitory Effect of Vitamin U (S-Methylmethionine Sulfonium Chloride) on Differentiation in 3T3-L1 Pre-adipocyte Cell Lines. Ann Dermatol. 2012; 24(1): 39-44. Doi: 10.5021/ad.2012.24.1.39.

31. Tunali S, Kahraman S, Yanardag R. Vitamin U, a novel free radical scavenger, prevents lens injury in rats administered with valproic acid. Hum. Exp. Toxicol. 2015; 34(9): 904-910.

32. Bayrak BB, et al. The protective effects of s-methyl methionine sulfonium chloride on brain tissue damage in D-galactosamine-induced hepatotoxicity. Experimed. 2022; 12(2): 38-43.

33. Vishakha DP, Hasumati AR, Nirav KG. Second Derivative Spectroscopic Method for Simultaneous estimation of Amiodarone Hydrochloride and Ranolazine in synthetic mixture. Asian J. Pharm. Ana. 2016; 6(1): 23-30. Doi: 10.5958/2231-5675.2016.00004.1

34. Turkyilmaz IB. Oxidative Brain Injury Induced by Amiodarone in Rats: Protective Effect of S-methyl Methionine Sulfonium Chloride. Acta Chim Slov. 2023; 20;70(1): 131-138. Doi: 10.17344/acsi.2022.7899.

35. Oktay S, et al. Effects of combined treatment of amiodarone and vitamine U on rats. Indian Journal of Experimental Biology. 2018; 56: 759-763.

36. Kusworini H, et al. Gingivitis on Systemic Lupus Erythematosus (SLE) patients: A Pilot study. Research J. Pharm. and Tech. 2020; 13(11): 5466-5470. Doi: 10.5958/0974-360X.2020.00954.3

37. Vidal's Handbook "Medicines in Russia" [online]. Available from: https://www.vidal.ru/drugs/gastrarex (Last accessed 09.01.2025).

38. Koksal E, et al. Controlled Release of Vitamin U from Microencapsulated Brassica oleracea L. var. capitata Extract for Peptic Ulcer Treatment. Food Bioprocess Technol. 2023; 16: 677–689. Doi: 10.1007/s11947-022-02965-3

Received on 11.01.2025 Revised on 06.05.2025

Accepted on 15.07.2025 Published on 01.12.2025

Available online from December 06, 2025

Research J. Pharmacy and Technology. 2025;18(12):5911-5916.

DOI: 10.52711/0974-360X.2025.00854

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