JLS and its natural extracts possess significant antioxidant properties. Studies indicate that JLS enhances the activity of key endogenous antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. This effect is particularly pronounced in cellular models of oxidative stress, such as HepG2, leading to effective scavenging of intracellular reactive oxygen species and protection against hydrogen peroxide-induced cell death [7]. The mechanism underlying this antioxidant effect involves the upregulation and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) [8]. Nrf2 is a master regulator of the cellular antioxidant response, and its activation leads to increased expression of downstream antioxidant enzymes, including NQO1 and HO-1, in human dermal fibroblasts. This suggests that the antioxidant effects of JLS are not merely due to direct scavenging of free radicals, but rather involve the activation of the body’s own defense mechanisms, providing more robust and sustained protection against oxidative stress. The activation of Nrf2 also contributes to enhanced collagen production, which may yield protective effects against photoaging. Furthermore, JLS has been shown to enhance the antioxidant and anti-inflammatory activities of various crop extracts, such as carrot leaf extracts, by increasing the content of phenolic compounds, including chlorogenic acid, caffeic acid, and cymaroside [9].

JLS possesses significant anti-inflammatory properties and often exerts synergistic effects when combined with other natural extracts. A notable study reported that JLS enhanced the anti-inflammatory activity of Litsea japonica fruit extract (LFE) in lipopolysaccharide-stimulated RAW 264.7 cells [10]. Combined treatment with JLS and LFE strongly inhibited nitric oxide (NO) production, and downregulated inducible NO synthase and cyclooxygenase-2 (COX-2) expression. Both NO and COX-2 are crucial pro-inflammatory mediators, and their suppression directly affects the inflammatory cascade. Mechanistically, this anti-inflammatory effect was mediated through the downregulation of the phosphorylation of mitogen-activated protein kinases (MAPKs), specifically ERK, JNK, and p38. MAPKs are central to cellular inflammatory responses and control the expression of numerous pro-inflammatory cytokines and enzymes [11]. By targeting these upstream pathways, JLS, particularly in synergistic formulations, exerts a wide range of anti-inflammatory effects that extend beyond reducing 1 or 2 inflammatory markers. Additionally, co-treatment suppressed the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-p65 and NF-κB inhibitor α (IκB-α), and mildly inhibited the degradation of IκB-α. Because NF-κB is a critical transcription factor involved in inflammatory processes, its modulation further contributes to anti-inflammatory outcome(s). The roles of Ca and Mg, however, are suggestive (based on related studies) and have not been directly confirmed for JLS [12], directly linking observed pharmacological effect to its mineral composition.

JLS is a highly valued ingredient in the cosmeceutical industry due to its diverse benefits for skin health. Its mineral-rich composition contributes to several key dermatological improvements. The minerals in JLS improve the intrinsic ability of the skin to retain moisture, leading to deeper and more prolonged hydration by increasing the expression of aquaporin-3 (AQP-3), CD-44, filaggrin, and caspase-14 in cultured keratinocytes (in vitro) and in a skin-equivalent ex vivo model [13]. This effect is supported by studies reporting increased expression of moisturizing factors, such as AQP-3, which facilitates water transport across cell membranes, and CD-44, a hyaluronic acid receptor, which promotes moisture retention in AQP-3-knockout mice [14]. Additionally, it increases the levels of filaggrin and caspase-14, which are involved in the generation of natural moisturizing factors [15]. The minerals present in JLS also help reinforce the skin barrier, making it more resilient and less susceptible to irritation and damage from environmental aggressors [16]. Silica and Mg play vital roles in collagen production and skin cell regeneration [17]. This enhances skin elasticity and firmness, which can reduce the appearance of fine lines and wrinkles. The calming properties of Mg specifically soothe irritated skin and reduce redness, making JLS particularly beneficial for sensitive skin types [12]. In addition to general skin health, JLS significantly inhibits melanogenesis [18]. It has been shown to safely and effectively inhibit α-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis in B16F10 melanoma cells. This action occurs through the modulation of the calcium/calmodulin-dependent protein kinase β (CaMKKβ)-5′ adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. The activation of AMPK, in turn, inhibits the signaling pathways of protein kinase A (PKA) and MAPKs, which are crucial for the expression of melanogenesis-related genes. The detailed molecular mechanism highlights its potential as a novel therapeutic agent for ameliorating skin pigmentation disorders.

JLS has demonstrated promising effects in addressing lifestyle-related diseases including diabetes, obesity, and cardiovascular conditions. Its mineral composition is often compared with that of deep-sea water, which has known benefits for these conditions. Electrodialyzed desalted ground seawater from JLS promotes insulin-induced glucose consumption in L6 muscle cells [19]. Some Jeju groundwater samples, particularly those containing vanadium, were found to stimulate glucose uptake in a vanadium-dependent manner, mimicking the effects of insulin. This finding suggests its potential role in improving glycemic control. Mineral-rich JLS inhibits lipid accumulation. Studies that optimized the Ca:Mg ratio in JLS found that a high Ca:Mg ratio (e.g., 5:1) effectively suppressed lipid accumulation in 3T3-L1 adipocytes [20]. This indicates that the precise balance of these key minerals -rather than their individual presence- is crucial for eliciting targeted biological responses. Furthermore, long-term intake of JLS (with hardness levels of 800 or 100 mg/L) significantly decreased epididymal adipose tissue weight and reduced adipocyte size in high-fat diet (HFD)-fed mice, suggesting its potent anti-obesity effects [21]. JLS also suppressed palmitate-induced intracellular fat accumulation in human hepatoma HepG2 cells and reduced hepatic fat accumulation in HFD-fed mice [7]. Deep seawater from Murotocape (Kochi, Japan) has been shown to have beneficial effects on hyperlipidemia and atherosclerosis in animal models [22]. Because the mineral composition of JLS is similar to that of deep-sea water,5 JLS is anticipated to have similar beneficial effects on hyperlipidemia and atherosclerosis.

JLS is a promising therapeutic agent for joint and bone health, particularly in osteoarthritis (OA). Balneotherapy, which involves bathing in JLS, has been investigated as a nonpharmacological treatment for knee OA [23]. In a rat model of knee OA, bathing in JLS significantly reduced joint thickness, improved mobility, increased bone mineral density of the joint, and decreased Mankin scores in the cartilage, collectively indicating a protective effect against cartilage degradation. The benefits of JLS for OA extend beyond its general anti-inflammatory effects to direct chondroprotective and chondrogenesis-promoting actions. This suggests its potential as a therapeutic agent for cartilage health via modulation of both anabolic and catabolic factors. In vitro studies investigating chondrocytes stimulated with pro-inflammatory cytokines revealed that treatment with JLS resulted in a concentration-dependent increase in the expression of anabolic factors (e.g., aggrecan, SOX9, and COL2A1), which are crucial for synthesis of cartilage matrix. Concurrently, it decreased the expression of catabolic factors (e.g., matrix-metalloprotein [MMP]3, MMP13, a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]4, and ADAMTS5), which are enzymes involved in cartilage degradation. We also observed synergistic effects when bathing in JLS was combined with diclofenac sodium, a conventional anti-inflammatory drug. Collectively, these findings suggest that bathing in JLS is a promising clinical intervention for knee OA. The biological effects of JLS are summarized in Table 2.

The diverse biological and pharmacological effects of JLS are intrinsically linked to its unique and rich mineral composition, which includes both macro-minerals and various trace elements. These minerals do not act in isolation. Rather, they frequently exhibit synergistic effects, and their combined action produces a greater benefit than the sum of their individual contributions. This implies complex, often interdependent, interactions in which the overall mineral balance -rather than just individual high concentrationsis crucial for bioactivity. The complexity of JLS-derived biological effects remains incompletely understood and, as such, requires further investigation.

Similar to deep-sea water, JLS may have extensive application possibilities across various industries, reflecting its recognized value and perceived health benefits [24]. The extensive industrial application of JLS across diverse sectors underscores its versatility and recognized value beyond simple hydration, driven by its unique mineral profile and perceived health benefits, indicating strong market acceptance based on observed efficacy. JLS is a prominent ingredient in numerous skincare products, including functional lotions, creams, gels, essences, and suncreams. These products are marketed for their enhanced hydration, antiaging, brightening, wrinkle improvement, skin regeneration, and anti-ultraviolet (UV) light properties. Several cosmetic products containing JLS have undergone clinical testing, demonstrating efficacy in blocking UV light (protection grade of UVA++++, sun protection factor 50+), skin tightening, and non-irritation. User reports have indicated noticeable improvements in skin hydration, radiance, and overall health. It is used in the production of potable salty groundwater, functional beverages, isotonic beverages, and mineral-enriched foods. It has been explored for use in functional foods such as Ca or Mg supplements. JLS has been incorporated into spa facilities, offering marine therapies and medical and recreational benefits aligned with the tourism industry. Balneotherapy, specifically bathing in JLS, has demonstrated promise in preclinical models of knee OA [23] by reducing joint thickness and improving mobility. JLS is also used in the manufacture of incense and other functional products. Its mineral richness makes it valuable for the cultivation of marine organisms and eco-friendly fruits and vegetables, thereby increasing their value-added potential.

The safety profile of JLS has been supported in previous studies [25,26], establishing it as a reliable ingredient for human applications. The consistent demonstration of safety across multiple in vitro and in vivo genotoxicity and oral toxicity models, provides a strong foundation for its continued use and expansion into human applications, particularly in the food and cosmetics sectors. JLS is inherently pure, clean, and naturally filtered to remove organic materials, pathogens, ammonia, nitrogen, and phenols. Studies have confirmed the absence of harmful heavy metals, such as mercury and cadmium [4], and it is reported to be free from other harmful substances. Studies investigating the genotoxicity of calcium derived from JLS have shown no mutagenic potential [25]. Bacterial reverse mutation assays, chromosomal aberration assays, and mammalian micronucleus tests performed at high concentrations (up to 5,000 mg/plate) have consistently yielded negative results, indicating that JLS does not directly damage DNA or chromosomes. Acute oral toxicity trials demonstrated that JLS exerted no adverse effects or mortality over a 14-day period in Sprague-Dawley rats. Furthermore, the subacute and subchronic oral administration of JLS did not result in significant changes in body weight, relative organ weight, or hematological or biochemical biomarkers [26]. These findings suggest that oral administration of JLS at relevant doses is safe in rats, providing a basis for its application. The safety and toxicity profiles of JLS are summarized in Table 3.