WO2022077276A1 - Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau - Google Patents

Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau Download PDF

Info

Publication number
WO2022077276A1
WO2022077276A1 PCT/CN2020/120924 CN2020120924W WO2022077276A1 WO 2022077276 A1 WO2022077276 A1 WO 2022077276A1 CN 2020120924 W CN2020120924 W CN 2020120924W WO 2022077276 A1 WO2022077276 A1 WO 2022077276A1
Authority
WO
WIPO (PCT)
Prior art keywords
skin
preparation
fermentum
lactobacillus fermentum
skin photoaging
Prior art date
Application number
PCT/CN2020/120924
Other languages
English (en)
Chinese (zh)
Inventor
赵欣
周先容
余建军
徐钦源
黄浩
Original Assignee
音芙医药科技(上海)有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 音芙医药科技(上海)有限公司 filed Critical 音芙医药科技(上海)有限公司
Priority to PCT/CN2020/120924 priority Critical patent/WO2022077276A1/fr
Priority to CN202080106065.8A priority patent/CN117377480A/zh
Publication of WO2022077276A1 publication Critical patent/WO2022077276A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants

Definitions

  • the invention belongs to the field of biomedicine, and in particular relates to the application of nicotinamide mononucleotide and Lactobacillus fermentum in combination in preparing a preparation for relieving skin photoaging.
  • the skin is one of the largest and most complex organs in the human body, accounting for about 15% of body weight, and it is also the first line of defense against various environmental aggressions.
  • Skin aging is an important part of body aging, which is not only detrimental to beauty, but also closely related to the occurrence of many skin diseases such as seborrheic keratosis, solar keratosis, basal cell carcinoma, and squamous cell carcinoma.
  • Photoaging refers to the premature aging of the skin caused by repeated light exposure, and its clinical manifestations, histopathological and biochemical changes are different from the natural aging of the skin.
  • Photoaging leads to a decrease in the number of mature type I collagen and elastic fibers in the dermis of the skin, and its clinical features are mainly manifested as skin roughness, loss of elasticity, deepening and thickening of wrinkles, leather-like appearance, and hyperpigmentation in exposed areas such as the face, neck, and forearm and telangiectasia.
  • NMSCs non-melanoma skin cancers
  • BCCs basal cell carcinomas
  • SCCs squamous cell carcinomas
  • Skin anti-aging has become a research hotspot of many scholars and clinicians in today's society, and it is also one of the hot areas that many beauty seekers pay attention to. In view of this, it is particularly important to establish a feasible photoaging model for in-depth study of its occurrence and development mechanism and screening of anti-photoaging drugs. Studies have shown that the occurrence and development of UV radiation-mediated skin photoaging involves multiple pathways, including apoptosis, proliferation, autophagy, DNA repair, checkpoint signal transduction, cell transduction, and inflammation.
  • UVA 315nm-400nm
  • UVB 280nm-315nm
  • UVC 200nm-280nm
  • UVB 280-315nm
  • UVB UVB radiation only accounts for 1-2% of the sun's ultraviolet rays, it is considered to be the main environmental carcinogen that causes skin cancer and is related to the occurrence and development of tumors.
  • the animal model is the most widely used photoaging model at home and abroad, and UVB is often used for modeling, because the skin tissue changes caused by UVB are very similar to human photoaging skin.
  • Nicotinamide ribonucleotide is synthesized from nicotinamide (Nic) and 5'-phosphate pyrophosphate by nicotinamide phosphotransferase (NAMPT) and is a key intermediate of NAD + .
  • NAMPT nicotinamide phosphotransferase
  • NMN has been shown to enhance NAD + biosynthesis and improve various pathologies in mouse disease models, such as myocardial and cerebral ischemia, neurodegenerative diseases such as Alzheimer's disease, and diabetes.
  • NMN nicotinamide mononucleotide
  • Lactobacillus fermentum is a gram-positive bacterium and is widely distributed in nature. They have important application value in important fields closely related to human life, such as industry, agriculture, animal husbandry, food and medicine.
  • the health benefits of Lactobacillus fermentum include regulating the immune system, regulating the balance of intestinal flora, lowering serum cholesterol and reducing the risk of tumors.
  • some Lactobacillus fermentum were found to have other important biological functions, such as anti-aging and antioxidant activities, attracting more and more researchers' attention.
  • Some studies have found that oral administration of live bacteria of Lactococcus lactis subsp. cremoris H61 or heat-killed bacteria can improve the skin condition of Japanese women.
  • the invention explores the relevant reagents for relieving skin photoaging, adopts UVB-induced skin damage mouse model, and then gives mice nicotinamide mononucleotide combined with L. fermentum bacterial suspension for gavage treatment, and finally through the oxidation of serum and skin index, inflammatory index, mRNA expression level and protein expression of related genes in skin and liver to evaluate the improvement effect of NMN combined with L. fermentum on UVB-induced skin damage in mice, so as to find new ways to prevent skin aging or develop NMN combined
  • the new probiotics of Lactobacillus fermentum provide theoretical reference and available raw materials.
  • the purpose of the present invention is to provide a new use of nicotinamide mononucleotide (NMN) combined with L. fermentum.
  • NPN nicotinamide mononucleotide
  • the first aspect of the present invention provides the application of nicotinamide mononucleotide in combination with Lactobacillus fermentum L. fermentum in the preparation of preparations for relieving skin aging.
  • the application of nicotinamide mononucleotide in combination with Lactobacillus fermentum in the preparation of preparations for relieving skin photoaging is provided, and the preparation forms include medicines, health products and skin care products.
  • Lactobacillus fermentum Lactobacillus fermentum form is different: when the preparation is a drug, health product or food additive, the Lactobacillus fermentum Lactobacilus fermentum is in the form of intermittently sterilized Lactobacillus fermentum cells or lysate; when the preparation is a skin care product When produced, Lactobacillus fermentum Lactobacilus fermentum is in the form of metabolites, cytoplasmic fragments, cell wall components or polysaccharide complexes of Lactobacillus fermentum.
  • the intermittently sterilized Lactobacillus fermentum cells are in the form of freeze-dried powder
  • the concentration ratio between the nicotinamide mononucleotide and the intermittently sterilized Lactobacillus fermentum cells is 1:1
  • the nicotinamide mononucleotide The concentration was 30 mg/mL
  • the concentration of Lactobacillus fermentum cells was 10 9 CFU/mL.
  • the photoaging skin is skin aging caused by ultraviolet radiation
  • the skin aging caused by ultraviolet radiation is skin photoaging induced by medium-wave ultraviolet radiation.
  • the preparation for relieving skin photoaging is a preparation for alleviating oxidative stress damage induced by ultraviolet radiation and reducing inflammatory damage in the body.
  • the preparation is an agent for activating the AMPK signaling pathway, thereby inhibiting the activation of the NF ⁇ B-p65 signaling pathway, and further reducing the damage of the body caused by oxidative stress and inflammatory responses.
  • the active ingredients of the preparation for relieving skin photoaging in the present invention only include nicotinamide mononucleotide and Lactobacilus fermentum.
  • the medicines for relieving skin photoaging are gels, ointments, emulsions, aerosols, injections, mixtures, oral ampoules, tablets or capsules;
  • the health care products for relieving skin photoaging are capsules, tablets, oral Liquid or solid beverages;
  • skin care products for relieving skin photoaging are liquids, creams, moisturizing powders or masks.
  • the present invention conducts experiments through the UVB-induced mouse skin injury model, and it is verified through experiments that NMN combined with L. fermentum activates the AMPK signaling pathway, thereby inhibiting the activation of the NF- ⁇ B signaling pathway and reducing the damage of inflammatory mediators to mice.
  • activated AMPK can reduce the oxidative damage of the skin and improve the overall antioxidant capacity of the body by regulating the levels of related oxidative stress indicators in the serum, liver and skin of mice. Therefore, the present invention has certain reference significance for the prevention and treatment of skin damage caused by UVB, and provides a theoretical basis and an available strain source for the development of the preparation of NMN combined with Lactobacillus fermentum.
  • Figure 1 is a comparison chart of the liver organ indexes of mice in different experimental groups. The data are presented as mean ⁇ standard deviation ( ⁇ SD), where * means p ⁇ 0.05, ** means p ⁇ 0.01, and *** means p ⁇ 0.001;
  • Figure 2 is the observation of the pathological morphology of the liver in different experimental groups
  • Figure 3 is the observation of skin pathological morphology in different experimental groups, (A) skin H&E staining; (B) skin Masson staining; (C) skin TB staining;
  • Figure 3 shows the mRNA expression levels of SOD1, SOD2, CAT and GSH in skin and liver tissues, data are presented as mean ⁇ standard deviation ( ⁇ SD), where * means p ⁇ 0.05, ** means p ⁇ 0.01, *** means p ⁇ 0.001;
  • Figure 4 shows the mRNA expression levels of AMPK, NF- ⁇ Bp65, I ⁇ B- ⁇ , SOD1 and CAT in skin and liver tissues, data are presented as mean ⁇ standard deviation
  • * means p ⁇ 0.05, ** means p ⁇ 0.01, *** means p ⁇ 0.001;
  • Figure 5 shows the mRNA expression levels of PGC-1 ⁇ , APPL1, mTOR, FOXO1, TNF- ⁇ , IL-6, IL-10 and GSH in skin and liver tissues, data are presented as mean ⁇ standard deviation
  • * means p ⁇ 0.05, ** means p ⁇ 0.01, and *** means p ⁇ 0.001.
  • NMN was provided by Yinfu Pharmaceutical Technology Co., Ltd. (Shanghai, China). The purity of NMN was determined by high performance liquid chromatography, and the purity was >98.5%.
  • Lactobacillus fermentum was isolated and purified from natural fermented yak yogurt in Xinjiang.
  • mice Forty 7-week-old female Kunming mice were purchased from the Experimental Animal Center of Chongqing Medical University [Chongqing, China, SCXK(YU) 2018-0003]. Mice were housed under constant temperature and humidity conditions (temperature 25 ⁇ 2°C, relative humidity 50 ⁇ 5%), 12h light/dark cycle. Mice were allowed free access to standard rat chow and drinking water.
  • mice Forty mice were randomly divided into 4 groups with 10 mice in each group, namely normal group, model group, VC group, and NMN+L.fermentum group (NMN+L).
  • the UVB modeling method is as follows: the whole experimental period is 4 weeks. From the 3rd week, the skin damage model of the mice in the other groups except the normal group is established by using ultraviolet radiation equipment, irradiating for 2h every day. Before UV irradiation, an electric shaver was used to shave about 2 cm 2 of hair on the back of the mice.
  • mice were administered free food and water; the mice in the VC group were given VC solution by gavage at a dose of 300 mg/kg.bw every day; Mice were orally gavaged with NMN, and at the same time, 1.0 ⁇ 10 9 CFU/mL bacterial suspension was orally administered to mice every day. All experiments were approved by the Chongqing Functional Food Collaborative Innovation Center.
  • Example 2 NMN+L.fermentum can improve liver organ index and tissue pathological morphology in mice after UV irradiation
  • mice After four weeks of culture, the mice were sacrificed by devertebral method, the mice were dissected to remove the liver and the hairless skin of the back of the mice, and the organ index of the liver was calculated. The results are shown in Figure 1.
  • liver and skin tissues were cut and fixed in 4% paraformaldehyde solution, and the remaining liver and skin tissues were stored in a -80°C refrigerator for later use.
  • the liver was stained with H&E and the skin was stained with H&E, Masson's trichrome and toluidine blue. Finally, an upright microscope was used to observe the pathological morphology of the tissue, and the results are shown in Figure 2 and Figure 3:
  • the mouse organ index can directly reflect the structural changes and functions of organs, and is of great significance for evaluating the functional properties of test samples.
  • the liver organ index of the mice in the model group was significantly reduced, indicating that UV irradiation not only directly accelerates skin aging, but also indirectly causes liver aging. oxidative stress or induced inflammatory response.
  • the liver organ index of the mice was significantly improved, indicating that NMN combined with L. fermentum can maintain the normal weight of the mouse liver and delay the aging of the liver.
  • the liver structure of the mice in the normal group was complete, and the hepatocytes were neatly arranged around the central vein in a satellite emission pattern.
  • the nuclei were large and round, and there was no infiltration of inflammatory cells.
  • the liver cells in the VC group were relatively disordered, with partial necrosis and infiltration of inflammatory cells around the central vein, and the overall structural integrity of the liver was worse than that in the normal group.
  • the phenomenon of cell infiltration; compared with the model group and the VC group, the shape of the liver cells in the NMN+L group was significantly more complete, and there was almost no cell necrosis and inflammatory cell infiltration, and the overall structure of the liver was similar to the normal group.
  • H&E staining is mainly used to observe the overall structure of the skin
  • Masson staining is mainly used to observe collagen fibers in the skin
  • TB staining is mainly used to observe mast cells in the skin.
  • the thickness of the skin dermis of the mice in the NMN+L group was significantly increased, and the collagen fiber bundles were not broken, shrunken and glued, and the overall structure was similar to that of the normal group.
  • Collagen fibers were blue-purple after Masson staining. It can be seen from Figure 3(B) that the normal group has a large number of collagen fibers, and the distribution is uniform and orderly. The number of collagen fibers in the model group was significantly less than that in the normal group, and the phenomenon of breakage and shrinkage appeared. The number of collagen fibers in the dermis of the skin of the mice in the VC group was less than that in the normal group, but higher than that in the model group. Compared with the model group and the VC group, the number of collagen fibers in the dermis of the mice in the NMN+L group increased more, the arrangement was more orderly, and there was almost no shrinkage or breakage.
  • the skin dermis of the UVB group mice became thinner, the number of collagen fibers decreased, the number of mast cells increased, and at the same time, the liver tissue also showed a certain degree of pathological changes, indicating that the UVB-induced skin damage model was successful.
  • the pathological morphology of the skin was greatly improved, and the liver of the mice also remained in a normal shape without obvious damage.
  • Example 3 NMN+L.fermentum can improve oxidative stress injury in UVB mice
  • Oxidative stress is one of the important factors of UVB-induced skin aging. Under normal circumstances, the generation and scavenging of oxygen free radicals are in a state of balance. When stimulated by the outside world, the body will generate a large amount of oxygen free radicals due to local hypoxia, resulting in cell apoptosis or damage.
  • Superoxide dismutase (SOD) is an enzyme containing metal cofactors, which can remove (disproportionate) the superoxide anion produced by the body and play an important role in the process of anti-aging and oxidation. With the progress of lipid peroxidation in the body, a large amount of SOD can be consumed, which in turn induces serious damage to the body.
  • Catalase is an enzyme scavenger, also known as catalase, which is a conjugated enzyme with iron porphyrin as a prosthetic group. It can promote the decomposition of H 2 O 2 into molecular oxygen and water, so as to protect cells from the poison of H 2 O 2 , and is one of the key enzymes in the biological defense system.
  • MDA is the final product of lipid oxidation. It can affect mitochondrial respiratory chain complexes and key enzyme activities in mitochondria in vitro. Its production can also aggravate membrane damage. Therefore, the determination of malondialdehyde content can reflect lipid peroxidation in the body. degree, which indirectly reflects the degree of cell damage.
  • Glutathione as an important antioxidant in the body, can scavenge free radicals in the human body; because GSH itself is susceptible to oxidation by certain substances, it can protect the sulfhydryl groups in many proteins and enzymes in the body It is not oxidized by harmful substances, so as to ensure the normal functioning of molecular physiological functions such as proteins and enzymes.
  • Advanced glycation end products AGEs are the end products of non-enzymatic glycation reactions, and their production and accumulation in serum and tissues increase with age. The protein modification of AGEs in the human body is closely related to the occurrence of senile diseases, so it can be used as an important indicator to test the aging process.
  • the skin When continuously exposed to UV light, the skin will produce a strong oxidative stress response, releasing a large amount of reactive oxygen species (ROS), and ROS as an upstream signal will further initiate the NF- ⁇ B-mediated inflammatory pathway, thereby making the skin appear dry , itching, erythema and edema and other inflammatory symptoms.
  • ROS reactive oxygen species
  • the nuclear transcription factor NF- ⁇ B and its inhibitory protein I ⁇ B are combined together and exist in the cell in a resting manner.
  • I ⁇ B- ⁇ is a repressor protein of NF- ⁇ B, which can mask the nuclear localization signal of NF- ⁇ B, so that NF- ⁇ B exists in the cell in the form of an inactive complex. Studies have shown that almost all NF- ⁇ B inducers rapidly activate NF- ⁇ B due to the degradation of I ⁇ B- ⁇ , so the activation of NF- ⁇ B can be prevented by preventing the phosphorylation of I ⁇ B- ⁇ .
  • TNF- ⁇ is a cytokine with a wide range of biological activities, which is mainly secreted by activated monocyte-macrophages and T cells, which can lead to the aggregation of inflammatory cells and stimulate the production of inflammatory cytokines by inflammatory cells, eventually leading to Inflammation.
  • IL-6 is a pleiotropic pro-inflammatory cytokine with biological activity, and its role is similar to IL-1 ⁇ . It can also activate the NF- ⁇ B signaling pathway to a certain extent, thereby causing chronic inflammation in the skin.
  • IL-6 can increase the permeability of the skin, allowing inflammatory factors to infiltrate the inflammatory site and initiate inflammation.
  • IL-10 is an important negative regulatory cytokine, which has a blocking effect on multiple links in the development of immune inflammatory response, has a wide range of immunosuppressive activities, and can inhibit the production of activated monocytes-macrophages
  • Other cytokines including IL1, IL6, granulocyte colony stimulating factor, TNF, platelet activating factor, etc. have strong immunosuppressive functions.
  • T-SOD, CAT, MDA and AGEs in mouse serum were determined according to the instructions of conventional biochemical kits, and the levels of TNF- ⁇ , IL-6 and IL-10 in mouse serum were determined according to the instructions of ELISA kits. The results are shown in the table. 1 shown.
  • T-SOD, CAT, Na + K + -ATP and NAD + in mouse serum were determined according to the instructions of conventional biochemical kits, and the levels of TNF- ⁇ and IL-10 in serum and skin tissue were determined according to the instructions of ELISA kits, respectively , and the results are shown in Table 2.
  • NMN combined with L. fermentum can increase the enzyme activities of T-SOD and CAT in serum and skin tissue of mice, increase the mRNA expression of SOD and CAT in liver and skin, and reduce the content of AGEs and MDA in serum.
  • NMN combined with L. fermentum can greatly increase the levels of T-SOD and CAT in serum, and the enzyme activity of T-SOD is even higher than that of the normal group.
  • the above results indicate that NMN combined with Lactobacillus fermentum can resist the oxidative stress of the skin caused by UVB irradiation in mice by increasing the activity of antioxidant enzymes, and can also improve the overall antioxidant level of the body from the levels of serum and liver.
  • NMN combined with L. fermentum can down-regulate the expression of pro-inflammatory cytokines TNF- ⁇ and IL-6 and up-regulate the expression of anti-inflammatory cytokine IL-10 from the serum level, skin tissue level and mRNA level, respectively, thereby reducing the The degree of inflammatory damage caused by these inflammatory mediators to skin-injured mice.
  • Example 4 NMN+L.fermentum can activate AMPK signaling pathway
  • AMP-activated protein kinase is a serine/threonine protein kinase, which is a heterotrimer formed by catalytic subunits ⁇ and ⁇ and regulatory subunit ⁇ . AMPK is mainly involved in the regulation of glucose, lipid and energy metabolism in the body. Studies have shown that AMPK activation can inhibit inflammation and oxidative stress.
  • AMPK can also act on nuclear transcription factor NF- ⁇ B and other inflammatory factors to regulate inflammation through various pathways, becoming a potential therapeutic target for various metabolic diseases such as diabetes and obesity and various inflammatory diseases.
  • NF- ⁇ B nuclear transcription factor
  • AMPK can effectively regulate the expression, migration and adhesion of inflammatory cytokines, thereby affecting the inflammatory response.
  • inhibition of AMPK activity can significantly enhance the expression of inflammatory factors such as TNF- ⁇ , IL-1 ⁇ , and IL-6, thereby aggravating inflammatory damage.
  • high expression of AMPK promotes the activity of factors such as SIRT1, FOXO, and PGC1 ⁇ , which in turn inhibits NF- ⁇ B activity. After cellular aging, NF- ⁇ B signaling is enhanced due to decreased AMPK activity.
  • Adiponectin receptor-binding protein belongs to the upstream gene of AMPK. It is a functional protein composed of 709 amino acids and located on chromosome 3. It can mediate a variety of cell signal transduction and play a role in a variety of cellular responses. It can regulate the inflammatory response of cells, anti-oxidation and arteriosclerosis.
  • Target of rapamycin mTOR is a downstream molecule in the AMPK signaling pathway, which mainly controls cell growth by regulating protein translation, and is involved in regulating cell immunity and apoptosis.
  • Activated AMPK can inhibit the activity of mTOR, inhibit the synthesis and translation of proteins, and then play a negative role in regulating tumor growth.
  • Activation of the mTOR pathway is thought to be closely related to the pathogenesis of cutaneous melanoma.
  • Forkhead transcription factor O1 (FOXO1) is a member of the forkhead box family, which is mainly involved in the regulation of various physiological and biochemical processes such as cellular oxidative stress, cycle arrest, autophagy, and metabolism.
  • peroxisome proliferator gamma coactivator alpha can participate in mitochondrial biosynthesis by regulating adaptive heat production, glucose and lipid metabolism, and blood sugar balance, and improve mitochondrial respiration and oxidation. ability to regulate fatty acid oxidation.
  • PGC-1 ⁇ can regulate the body's adaptive heat production, glucose and lipid metabolism and blood sugar balance, participate in mitochondrial biosynthesis, and improve mitochondrial respiration and oxidation capacity.
  • NMN combined with L. fermentum is used to display the related factors in the AMPK signaling pathway and the level changes of the related factors through this signal.
  • the experimental method was as follows: liver and skin tissues were homogenized and total RNA was extracted with Trizol reagent, and then the RNA was reverse transcribed into cDNA using a cDNA kit. Next, 1 ⁇ L of cDNA, 10 ⁇ L of TaqMan TM Multiplex Master Mix, 2 ⁇ L of 10 ⁇ M primer and 7 ⁇ L of ddH 2 O were mixed evenly, and amplification detection was performed on a real-time fluorescence quantitative PCR instrument.
  • the amplification conditions were: deformation at 95°C for 15s, annealing at 55°C for 30s, and extension at 72°C for 35s, for a total of 40 cycles. Finally, the relative expression of each target gene was calculated by 2 - ⁇ CT , in which ⁇ -actin was used as an internal reference gene.
  • the primer sequences used are shown in Table 3.
  • Figure 4 shows the mRNA expression of AMPK, NF- ⁇ B p65, I ⁇ B- ⁇ , SOD1 and CAT in skin and liver tissues.
  • UVB irradiation increased the mRNA expression levels of NF- ⁇ Bp65 in the skin and liver of mice, and decreased the expressions of I ⁇ B- ⁇ , AMPK, SOD and CAT, among which the model group had the most obvious changes. .
  • the mRNA expressions of I ⁇ B- ⁇ , AMPK, SOD and CAT in the skin and liver of the VC group and the NMN+L group were increased to varying degrees, while the expression of NF- ⁇ Bp65 was decreased, among which NMN+
  • the mRNA expression levels of the above indicators in the L group were close to those in the normal group.
  • AMPK mRNA and protein in the liver and skin of mice in the model group was significantly lower than that in the normal group, indicating that UVB irradiation caused energy metabolism disorders in mice, and increased oxidative stress and inflammatory responses.
  • NMN combined with L. fermentum gavage treatment can significantly increase the mRNA expression of AMPK in liver and skin tissues, indicating that NMN combined with L. fermentum can effectively promote cellular energy synthesis and reduce the damage caused by oxidative stress and inflammatory reactions.
  • Figure 5 shows the mRNA expression levels of PGC-1 ⁇ , APPL1, mTOR, FOXO1, TNF- ⁇ , IL-6, IL-10 and GSH in skin and liver tissues.
  • the mRNA expressions of PGC-1 ⁇ , APPL1, FOXO1, IL-10 and GSH in the skin and liver of the normal group mice were the highest, and the expressions of mTOR, TNF- ⁇ and IL-6 were the lowest, while the model Compared with the normal group, the expression levels of the above indexes in the skin and liver of the mice in the group showed a completely opposite trend, and there were significant differences between the two.
  • VC and NMN combined with L.
  • UVB irradiation can reduce the mRNA expression of APPL1, FOXO1 and PGC-1 ⁇ and increase the mRNA expression of mTOR in mouse skin and liver.
  • the mRNA expressions of APPL1, LKB1, SIRT1, FOXO1 and PGC-1 ⁇ in the skin and liver of mice were significantly increased, while the mRNA expression level of mTOR decreased, indicating that NMN combined with L. fermentum can effectively By activating the AMPK signaling pathway, it can improve UVB-induced oxidative stress and inflammation in mice.
  • NMN combined with L. fermentum has a relatively obvious improvement effect on UVB-induced skin damage in mice.
  • the possible mechanism may be combined with NMN and L. fermentum by activating the AMPK signaling pathway, thereby inhibiting the activation of the NF- ⁇ B signaling pathway, and reducing the damage of inflammatory mediators to mice.
  • activated AMPK can reduce the oxidative damage of the skin and improve the overall antioxidant capacity of the body by regulating the levels of related oxidative stress indicators in the serum, liver and skin of mice.
  • This study has important reference significance for the prevention and treatment of UVB-induced skin damage, and provides a theoretical basis and available strain sources for the development of NMN combined with Lactobacillus fermentum health food.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne une application d'une combinaison de nicotinamide mononucléotide (NMN) et de Lactobacillus fermentum (L. fermentum) dans la préparation d'une formulation pour soulager le photovieillissement de la peau. Des expériences vérifient que NMN et L. fermentum sont combinés pour activer la voie de signalisation AMPK, de manière à inhiber l'activation de la voie de signalisation NF-κB, ce qui permet de réduire les dommages d'un milieu inflammatoire à une souris. De plus, l'AMPK activée peut réduire les dommages oxydatifs de la peau et améliorer la capacité antioxydante globale d'un corps en ajustant les niveaux d'indicateurs de stress oxydatif associés dans le sérum, le foie et la peau d'une souris. Par conséquent, la présente invention a une certaine importance de référence pour la prévention et le traitement de dommages cutanés induits par les UVB, et fournit une base théorique et des sources de souches disponibles pour le développement d'une formulation combinée de NMN et de L. fermentum.
PCT/CN2020/120924 2020-10-14 2020-10-14 Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau WO2022077276A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/CN2020/120924 WO2022077276A1 (fr) 2020-10-14 2020-10-14 Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau
CN202080106065.8A CN117377480A (zh) 2020-10-14 2020-10-14 烟酰胺单核苷酸与发酵乳杆菌联合在制备缓解皮肤光老化制剂中的应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2020/120924 WO2022077276A1 (fr) 2020-10-14 2020-10-14 Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau

Publications (1)

Publication Number Publication Date
WO2022077276A1 true WO2022077276A1 (fr) 2022-04-21

Family

ID=81207547

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/120924 WO2022077276A1 (fr) 2020-10-14 2020-10-14 Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau

Country Status (2)

Country Link
CN (1) CN117377480A (fr)
WO (1) WO2022077276A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115960742A (zh) * 2022-07-12 2023-04-14 广东省科学院微生物研究所(广东省微生物分析检测中心) 具有延长真皮成纤维细胞寿命、抗皮肤老化功能的发酵乳杆菌xjc48及其应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015186114A1 (fr) * 2014-06-06 2015-12-10 Glaxosmithkline Intellectual Property (No.2) Limited Analogues de nicotinamide riboside, compositions pharmaceutiques et leurs utilisations
CN108430482A (zh) * 2015-11-10 2018-08-21 伊丽莎白·麦克纳 细胞氧化还原水平的控制
CN110507672A (zh) * 2019-08-28 2019-11-29 杜斌 一种高效微生态调整剂及其应用
CN111035012A (zh) * 2019-12-16 2020-04-21 青岛赛珥生物医学科技有限公司 一种抗氧化营养组合胶囊及其制备方法
CN111246838A (zh) * 2017-10-06 2020-06-05 艾克斯奥巴德蒙公司 用于将活性成分递送至皮肤的套件
WO2020150329A1 (fr) * 2019-01-15 2020-07-23 Microbiome Labs, Llc Composition probiotique à base de spores pour la modulation de propriétés dermiques et sous-dermiques
CN111511379A (zh) * 2017-12-06 2020-08-07 Lac2生物群系有限公司 基于益生菌的组合物及其应用

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015186114A1 (fr) * 2014-06-06 2015-12-10 Glaxosmithkline Intellectual Property (No.2) Limited Analogues de nicotinamide riboside, compositions pharmaceutiques et leurs utilisations
CN108430482A (zh) * 2015-11-10 2018-08-21 伊丽莎白·麦克纳 细胞氧化还原水平的控制
CN111246838A (zh) * 2017-10-06 2020-06-05 艾克斯奥巴德蒙公司 用于将活性成分递送至皮肤的套件
CN111511379A (zh) * 2017-12-06 2020-08-07 Lac2生物群系有限公司 基于益生菌的组合物及其应用
WO2020150329A1 (fr) * 2019-01-15 2020-07-23 Microbiome Labs, Llc Composition probiotique à base de spores pour la modulation de propriétés dermiques et sous-dermiques
CN110507672A (zh) * 2019-08-28 2019-11-29 杜斌 一种高效微生态调整剂及其应用
CN111035012A (zh) * 2019-12-16 2020-04-21 青岛赛珥生物医学科技有限公司 一种抗氧化营养组合胶囊及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHAO CAN, WENJING LI, HAOYUN DUAN, ZONGYI LI, YANNI JIA, SONGMEI ZHANG, XIN WANG, QINGJUN ZHOU, WEIYUN SHI: "NAD+ precursors protect corneal endothelial cells from UVB-induced apoptosis", AM J PHYSIOL CELL PHYSIOL, vol. 318, 12 February 2020 (2020-02-12), pages C796 - C805, XP055922680, DOI: 10.1152/ajpcell.00445.2019 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115960742A (zh) * 2022-07-12 2023-04-14 广东省科学院微生物研究所(广东省微生物分析检测中心) 具有延长真皮成纤维细胞寿命、抗皮肤老化功能的发酵乳杆菌xjc48及其应用

Also Published As

Publication number Publication date
CN117377480A (zh) 2024-01-09

Similar Documents

Publication Publication Date Title
WO2022001784A1 (fr) Application d'un inhibiteur de glutaminase dans la préparation d'un médicament pour traiter le psoriasis
CN109125107B (zh) 一种有效改善和修复面部激素依赖性皮炎的多肽组合物
CN106539092A (zh) 一种绿藻多糖化纳米硒及其制备方法与应用
WO2023005265A1 (fr) Application d'un mélange de nucléotides dans la préparation de formulations pour la prévention ou le soulagement de la sarcopénie sénile
Liu et al. Molecular mechanisms of anti-cancer bioactivities of seaweed polysaccharides
Wu et al. Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing
Zhou et al. Nicotinamide mononucleotide combined with lactobacillus fermentum TKSN041 reduces the photoaging damage in murine skin by activating AMPK signaling pathway
US20150140112A1 (en) Composition comprising extract of mixture of undaria pinnatifida sporophylls and ascidian shells for treating atopic dermatitis
WO2022077276A1 (fr) Application d'une combinaison de nicotinamide mononucléotide et de lactobacillus fermentum dans la préparation d'une formulation pour soulager le photovieillissement de la peau
WO2018175334A1 (fr) Compositions et méthodes de traitement d'affections cutanées
CN111870609A (zh) 一种肠道菌群调节剂及其应用
CN102008083B (zh) 一种缓解体力疲劳、祛黄褐斑的保健食品
CN103897010B (zh) 一种用于治疗银屑病的组合物及制备方法
WO2022047779A1 (fr) Utilisation de nicotinamide mononucléotide dans la préparation d'un réactif permettant d'améliorer le niveau d'enzyme na+-k+-atp dans un sarcolemme de peau lésée
KR20100059305A (ko) 저실자 추출물 함유 피부외용제 조성물
Onogawa et al. Animal studies supporting the inhibition of mast cell activation by Eriobotrya japonica seed extract
Lan et al. Vitamin e succinate inhibits the growth of human gastric cancer cells
Murray Pyrroloquinoline quinone (PQQ): The next essential nutrient and supplement superstar
CN114831312B (zh) 一种由灵芝多糖和金蝉花多糖构成的中药组合物及应用
WO2023155865A1 (fr) Utilisation d'oligosaccharides de morinda officinalis et composition de ceux-ci dans la prévention ou le traitement de la dépression
Buranasudja et al. DNA Damage and Energy Crisis are Central in the Mechanism for the Cytotoxicity of Pharmacological Ascorbate in Cancer Treatment
CN112972391B (zh) 一种胆红素-jph203纳米颗粒及其制备和应用
WO2022073437A1 (fr) Utilisation de cannabidiol et sa combinaison avec un extrait de nid d'oiseau comestible dans l'hydratation et l'humidification de la peau
Cavalchini et al. Complementary treatment of psoriasis with an AFA-phyocyanins product: a preliminary 10-cases study
CN105287777B (zh) 一种利尿的药物组合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20957057

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 202080106065.8

Country of ref document: CN

122 Ep: pct application non-entry in european phase

Ref document number: 20957057

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205 DATED 20.09.2023)