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![The characterization and classification of humic substances. Adapted from [5]. (a) Humic substances are isolated from various parent material like peat, coal, water, and soil through a series of precipitation/dissolution steps; their general characteristics are highlighted in each box [9, 10]. (b) Proposed composition of fulvic acid by Health Canada.](publication/327578277/figure/fig1/AS:1086447536877568@1636040686008/The-characterization-and-classification-of-humic-substances-Adapted-from-5-a-Humic.jpg)
The characterization and classification of humic substances. Adapted from [5]. (a) Humic substances are isolated from various parent material like peat, coal, water, and soil through a series of precipitation/dissolution steps; their general characteristics are highlighted in each box [9, 10]. (b) Proposed composition of fulvic acid by Health Canada.
Source publication
Chronic inflammatory diseases like diabetes are on a rise in the Western world. Based on the tsunami of new cases every year, new therapeutic measures must be considered. A promising avenue might involve the attenuation of underlying inflammation through natural health products (NHPs). This is because most NHPs have a rich history in traditional me...
Citations
... The bioactive compounds present in Shilajit have shown therapeutic potential in managing various health conditions, including metabolic, respiratory, neurological, musculoskeletal, and reproductive disorders. Notably, it has been studied for its benefits in conditions such as osteoarthritis, anemia, diabetes, and Alzheimer's disease [21][22][23]. Shilajit, when administered orally following tibia fracture surgery enhanced bone regeneration, according to an Iranian clinical trial [24]. Nevertheless, studies on shilajit's direct impact on hPDL cells' capacity for wound healing are lacking. ...
Background
Shilajit is a pale-brown to blackish-brown fluid that varies in consistency and is released from rock layers in various mountain ranges across the world. For thousands of years, traditional medical systems in several nations have included shilajit in one form or another as a rejuvenator and adaptogen. Numerous medicinal qualities have been attributed to it, several of which have been confirmed by contemporary scientific analysis. This in vitro study was established to investigate the effect of shilajit on human Periodontal ligament (hPDL) cell wound closure.
Methods
The cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)—2,5-diphenyltetrazolium bromide tetrazolium reduction (MTT) test following a 24-hour exposure of shilajit. With the use of an inverted phase contrast microscope, morphological alterations were noted. Acridine orange/ethidium bromide dual labeling, to evaluate the apoptotic cell death in shilajit treated cells. An in vitro wound healing test was utilized to evaluate wound healing in wounded hPDL cell monolayers for 24 h in the presence or absence of shilajit. The Matrix metalloproteinases-2 and 9 (MMP-2 and MMP-9) in hPDL cells treated with shilajit were measured using the enzyme-linked immunosorbent assay (ELISA) technique, and real-time PCR was used to examine gene expression linked to wound healing and apoptosis.
Results
Shilajit’s cytotoxicity evaluation on hPDL cells showed that dosages as high as 3 mg/mL had no adverse effects and maintains the cell viability, suggesting a possible stimulatory effect on cell growth. Cell viability was reduced significantly (p < 0.05) by dosages more than 4 mg/mL, indicating cytotoxicity at higher concentrations. According to the scratch wound healing assay, shilajit administration at doses of 2 and 3 mg/mL accelerated wound healing and improved cell migration in hPDL cells. Shilajit promoted a controlled inflammatory response and supported periodontal ligament healing by upregulating the expression of genes involved in collagen synthesis, collagen type I alpha 1 chain (COL1A1) and pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and, interleukin-1-beta (IL-1β), according to real-time PCR data. In addition, Shilajit raised the protein levels of MMP2 and MMP9, two important enzymes involved in tissue remodeling. Shilajit-treated hPDL cells showed a substantial increase of cell proliferation and no discernible apoptotic activity.
Conclusions
Our research offers novel proof that shilajit promotes hPDL cell migration and proliferation, which in turn promotes wound closure. According to these results, Shilajit may improve tissue regeneration, accelerate wound healing, and encourage the growth of periodontal ligament cells.
... It has been traditionally used in treatments for skin conditions such as eczema and dermatitis, often in the form of water-insoluble creams or patches (Beer et al., 2003;Kovalenko et al., 2016;Obuka et al., 2018;Rumyantsev et al., 2017;Stankevica & Klavins, 2014;Wollina, 2009). This naturally formed sapropel consists mainly of humic substances (HSs) and non-humic substances, all of which have demonstrated biological activity (García-Villén et al., 2018;Winkler & Ghosh, 2018;Wollina, 2009). Humic substances are categorized into four fractions: humic acid (HA), hymatomelanic acid (HMA), fulvic acid (FA), and humin. ...
Sapropel, a sediment rich in organic matter and bioactive compounds, has significant potential for pharmaceutical and cosmetic applications. This study aimed to develop a stable, water-soluble hydrogel containing sapropel extract as a delivery platform for these bioactive compounds. Sodium carboxymethylcellulose (Na-CMC) was used as a gelling agent in eight formulations, with or without sapropel extract, and buffer solutions (NaCl, MgSO4, MgCl2). The gels were evaluated for organoleptic properties, pH, viscosity, stability, and thermal resistance over a 2-year period under different storage conditions.
All sapropel extract containing formulations exhibited a smooth, homogeneous and light-yellow appearance with good stability and spread ability. The pH levels ranged from 4.7 to 7.4, within the acceptable range for skin application, although formulations with MgCl2 showed greater pH fluctuations. Viscosity analyses revealed that sapropel extract decreased viscosity, particularly under fluctuating temperatures. MgSO4-buffered formulations exhibited the most stable viscosity over time. However, some formulations demonstrated decreased stability and viscosity after prolonged exposure to elevated temperatures and UV light. Centrifugal and thermal tests confirmed the physical stability of the gels, with no phase separation observed.
Overall, the study confirms the feasibility of incorporating sapropel extract into stable, water-soluble hydrogels, making them suitable for potential therapeutic and cosmetic uses.
... Natural polyelectrolytes are of interest in the development of new drug delivery systems as a replacement for synthetic carriers, which are more expensive and less environmentally friendly 9 . An example of such natural polyelectrolytes is humic acids (HAs) and fulvic acids (FAs), which have great potential for medical use 10,11 . Humic substances (HS) are heterogeneous, polydisperse mixtures consisting of polymer structures that are formed in soils, bottom sediments, and natural waters during the destruction of microbial and plant residues 12 20 . ...
Earlier, we showed (Morozova M.A. et al., 2022) that solutions of the humic acids (HAs) and fulvic acids (FAs) complex used as a solvent are applicable for increasing the solubility and colloidal stability of antiviral drugs. In this study, we investigated the ability of humates to form stable colloidal systems with chelated zinc complexes with amino acids. The study of the dispersion properties of the samples was carried out using the dynamic light scattering (DLS) technique. There were obtained HAs and FAs dilutions that form a colloidal solution with zinc chelate complexes with specified characteristics of particle size and zeta potential. The solutions contained mainly 20 nm nanoparticles and their zeta potential was -24 mV. The toxicity was assessed using the Spirotox method. A comparative toxicological analysis of zinc valinate samples dissolved in HAs and water showed that the use of HAs as an adjuvant allows for a radical decrease in the toxicity of zinc chelate. Keywords: extract of humic substances; fulvic acid; zinc chelate complexes; zincvalinate; toxicity; Spirotox-method
... Fulvic acid is also the main component of Shilajit, an organic mineral product that has been applied in the field of Ayurvedic traditional medicine for a long time [64]. The actions of fulvic acid in the body have been summarized in previous reports as immunomodulatory, oxidation-regulating, and gastrointestinal-activating, and it has been found to promote the activation of various physiological functions [65]. Regarding anticancer effects, fulvic acid is considered to prevent the progression of cancer by inhibiting the proliferation of cancer cells and inducing apoptosis [66,67]. ...
Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with supplementation with natural products may confer benefits to cancer patients, by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.
... In the meantime, different studies have confirmed the anti-inflammatory and neoplastic functions of humic substances (22)(23)(24). On the other hand, the antiinflammatory and anti-allergic effects of fulvic acid have also been proven in sensitized mast cells and basophils (25). Interestingly, fulvic acid can reduce the release of proinflammatory mediators and TNF-α expression in U937 cells. ...
Background: Shilajit is a natural pale-brown to blackish-brown phytocomplex that exudes from mountain rocks in various parts of the world. In recent years, numerous pharmacological effects of shilajit have been explored through extensive experiments. Shilajit is known as an antioxidant and anti-inflammatory agent. Activation of the nuclear factor kappa B (NF-κB) signaling pathway could be an important player in inflammation-driven tumor progression. Therefore, the current study evaluated the anti-inflammatory effect of shilajit on a breast cancer cell line (MCF7). Methods: In this experimental study, the MCF7 cell line was treated with shilajit, and an MTT assay was applied to analyze the half-maximal inhibitory concentration (IC50) after 72 hours of treatment. Following this, the apoptotic rate was assessed using flow cytometry, and p50, RelB, and IKKα/β gene expression were evaluated using real-time PCR assay. Results: Shilajit had potent cytotoxic activity in a dose- and time-dependent manner with an IC50 of 280 μg/mL. Based on the Annexin-PI analysis, the IC50 concentration of this compound induced significant apoptosis in the cells, possibly through suppression of NF-κB (p50, RelB, and IKKα/β)-regulated genes. The real-time PCR results indicated that treating MCF7 cells at the IC50 dose of shilajit for 72 hours could reduce the mRNA expression levels of p50, RelB, and IKKα/β in the cells. Conclusion: The findings of the present experiment showed that shilajit may have promising anti-breast-tumor and anti-inflammatory activity through inhibition of the NF-κB signaling pathway. Therefore, shilajit can help treat breast cancer in combination with other standard treatments.
... Thus, the adsorbed containments can stimulate movement, settling, stability, fate, reactivity, bioavailability, and toxic behavior of MPs/NPs . For instance, MPs and NPs can intermix with salts, organic chemicals, heavy metals, and, lipids, proteins, natural organic matter (NOM) including, humic acid (HA), fluvic acid (FA), extracellular polymeric substances (EPS, exuded from bacteria, plants, algae, and microbes), and other biomolecules (proteins, DNA, lipids, RNA, amino acids, saliva) (Giri and Mukherjee, 2021;Ma et al., 2022;Shiu et al., 2020;Wu et al., 2021a;Xiong et al., 2020) and they can form "eco/bio-coronas-based MPs/NPs complex" or "biogenic aggregation" in the environment because both NOM or biomolecules and plastic particles possess unique physico-chemical characteristics in terms of weights, molecular sizes, surface charges, shapes, and surface properties (Levchuk et al., 2018;Pradel et al., 2021;Winkler and Ghosh, 2018;Yu et al., 2021). ...
Microplastics (MPs) and nanoplastics (NPs) have been discovered in diverse environmental milieux, and they have attracted much attention due to their possible toxicological impacts on living organisms. Likewise, salts, organic chemicals, heavy metals, natural organic matter, and other biomolecules are ubiquitously in the ecosystem. In a natural environment, MPs and NPs can interact with natural organic matter and biomolecules because of their exceptional characteristics. They can develop corona-based complexes, including eco-corona (EC) or bio-corona (BC) on the surface of MPs and NPs that not only change physiochemical characteristics but also its fate, distribution, uptake, transportation, biotransformation, and toxicological performance. Unlike orthodox toxins, coronas-based complexes on MPs and NPs rather than pristine MPs/NPs may be more hazardous. Therefore, the current critical review aims to discuss the up-to-date status of the modulations in the toxicological behavior of coronas-based MPs and NPs complexes on different environmental species. Significantly, it also focuses on the factors affecting the modulations of toxicological behavior of eco- and bio-corona-based MPs and NPs complexes for better understanding the role of environmental variables on the toxicity of plastics particles. Furthermore, this review systematically highlighted that the effect of a coronas-based complexes on the toxicological behavior of MPs and NPs is multifarious and variable in terms of plastic particle sizes, biomolecule’s types, polymer types, environmental species, and designed experimental conditions. To sum up, the current review addresses existing knowledge gaps and suggests recommendations.
... Sapropel sediments have an antioxidant effect that smooths wrinkles, prevents new wrinkles, and smooths the skin structure, as well as removing swelling and strengthening nails and hair [4,5]. Therefore, the therapeutic effect of sapropel helps to maintain the cellular structure of the skin [6,7] and restore immunity and helps with acne, rashes, and dermatitis [8,9]. In addition, balneotherapy has shown healing capabilities in the treatment of various musculoskeletal and rheumatologic diseases [10]. ...
... The investigated sapropel extracts have relatively high AO activity and TPC in various lake samples, which is in accordance with studies reported by Obuka and co-workers [27]. Sapropel extracts show a high polyphenol content, and this has a strong correlation with the TAS, so polyphenols in sapropel extracts are responsible for AO activity [9,28]. The high TPC content may allow sapropel extracts to represent a prospective preparation for the treatment of skin diseases and complex wounds [29,30], as well as for local applications to people suffering from long-healing wounds/injuries (e.g., type II diabetes patients) [8,9], as these wounds do not heal quickly, form scar tissues, and are prone to inflammation. ...
... Sapropel extracts show a high polyphenol content, and this has a strong correlation with the TAS, so polyphenols in sapropel extracts are responsible for AO activity [9,28]. The high TPC content may allow sapropel extracts to represent a prospective preparation for the treatment of skin diseases and complex wounds [29,30], as well as for local applications to people suffering from long-healing wounds/injuries (e.g., type II diabetes patients) [8,9], as these wounds do not heal quickly, form scar tissues, and are prone to inflammation. ...
Background and Objective: Sapropel, a biologically active sedimentary deposit, is high in organic matter and minerals and has been shown to offer health benefits. Its constituents, humic acid (HA) and fulvic acid (FA), have been found to have some therapeutic applications. The aim of this study was to determine the potential therapeutically significant properties of freshwater sapropel extracts: their polyacid content, antioxidative (AO) status, and biological activity in cell culture. Materials and Methods: Freshwater lakes from the southeast region of Latvia were investigated layer by layer. The total organic carbon (TOC) was determined through combustion using the catalytic oxidation method, HA and FA were measured via acid perspiration, and the total polyphenol content (TPC) and total antioxidant status (TAS) was analysed spectrophotometrically. Sapropel extracts’ regenerative abilities were tested in vitro using a Cell-IQ real-time monitoring system on mouse BALB/c 3T3 fibroblasts and human keratinocyte HaCaT cell lines. Cytotoxicity was measured through neutral red uptake assessment as a concentration-dependent reduction in the uptake of neutral red dye relative to a vehicle control or untreated cells. Results: The highest AO activity was observed in sapropel extracts with elevated concentrations of HA and TPC from Audzelu Lake (1.08 ± 0.03 mmol/L), and the lowest activity was found in extracts from Ivusku Lake (0.31 ± 0.01 mmol/L). Correspondingly, the concentrations of HA in Audzelu and Ivusku Lakes were recorded as 45.2 and 27.4 mg/g, respectively. High concentrations of HA promoted in vitro cell growth upon short-term exposure (up to 6 h). Conclusions: The results show that high TPC correlates with AO status and sapropel extracts with higher concentrations of HA exhibit greater AO activity and promote in vitro cell growth, suggesting a perspective use for short-term topical therapeutic skin applications. However, higher concentrations over longer durations showed cytotoxic effects, indicating the need for further investigation.
... Fulvic acid is also the main component of Shilajit, which has been applied in the field of Ayurvedic traditional medicine for a long time 44 . The actions of fulvic acid in the body have been summarized in previous reports as immunomodulatory, oxidationregulating, and gastrointestinal-activating, and it has been found to promote the activation of various physiological functions 45 . Regarding anticancer effects, fulvic acid is considered to prevent the progression of cancer by inhibiting the proliferation of cancer cells and inducing apoptosis 46,47 . ...
Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.
... Because FA decrease proinflammatory markers but also activate the immune system to kill bacteria. It is shown to reduce oxidative stress and even induce apoptosis in hepatic cancer lines, it is considered an antiseptic and analgesic (Meena et al., 2010;Winkler and Ghosh, 2018). ...
... Animal studies show that fulvic acid can increase immune defenses and antioxidant activity, and decrease inflammation. [24,25] Research has shown that fulvic acid increases the expression of interleukin (IL)-10, one of the most important antiinflammatory cytokines. Positive regulation of IL-10 accelerates wound healing. ...
... [27] The increase in the incidence of wounds and the variety of treatment approaches has led researchers to search for a simple, inexpensive treatment with the fewest side effects. Despite previous experiences with the use of soils containing humic or fulvic acid, [20][21][22][23][24][25][26][27][28][29][30] the combined effect of humic and fulvic acid has not been studied simultaneously. The aim of this study was to investigate the efficacy of coadministration of HA and fulvic acid in wound healing in a rat animal model. ...
... Also, mention that no bacteriological information was collected (as fulvic acid is known to be effective against MRSA and Pseudomonas). 25.00 ± 4.10* *P < 0.01 compare with control and sham groups ...
Background
Finding new compounds to accelerate wound healing is critical today. Humic substances or fulvic acid each have anti-inflammatory properties.
Aims and Objectives
The purpose of this study is to determine the effects of poultice 0.5% containing humic and fulvic acids on wound healing in male rats.
Materials and Methods
An animal model was arranged by making a full-thickness skin wound was created in each rat. Animals were randomly divided into control, sham, and treatment groups. To investigate the effect of humic and fulvic acids combining poultice, the wound area and histological analyses of the number of inflammatory cells, fibroblasts, and angiogenesis were evaluated for 21 days.
Results
The animals in the treated group showed higher wound healing percentage, angiogenesis, and fibroblast distribution compared with the control ( P < 0.001). Moreover, the topical administration of humic and fulvic acids 0.5% poultice decreased the mean number of inflammatory cells significantly than the other groups ( P < 0.001).
Conclusion
The topical administration of a poultice containing humic and fulvic acid accelerated wound healing by increasing angiogenesis and fibroblast and reducing inflammatory cell distribution in a rat model.
