Novel Targets and Potential Mechanisms of Mizuhopecten yessoensis-Derived Tripeptide NCW as Antihypertensive Peptides.

SCOPE: Mizuhopecten yessoensis-derived tripeptide Asn-Cys-Trp (NCW) exhibits a potent antihypertensive effect in vivo. However, a lack of knowledge of the antihypertensive mechanism of tripeptide NCW limits its application for functional foods industrialization. The purpose of this study is to elucidate the corresponding targets and mechanisms of tripeptide NCW in hypertension regulation. METHODS AND RESULTS: Administration of tripeptide NCW for 3 weeks, the blood pressure of spontaneously hypertensive rats (SHRs) is significantly decreased. After sacrifice, the serum sample is analyzed using tandem mass tag (TMT)-based liquid chromatography with tandem mass spectrometry to identify differentially expressed proteins. The proteomic analysis indicates that tripeptide NCW administration alters serum protein profiles in SHR rats, significantly upregulating 106 proteins and downregulating 30 proteins. These proteins enhance the glycolysis, glucose, and TCA cycle, improve amino metabolism, trigger the cAMP/PKA, cGMP/PKG, PI3K/AKT, and AMPK signal pathways, and inhibit Ras-regulated JNK activation, TGF-ß/MAPK, and TGF-ß/ RhoA/ROCK pathways. CONCLUSION: Tripeptide NCW supplementation is demonstrated to regulate signal pathways involved in the control of blood pressure and regulate the energy and amino acids metabolic processes in serum, providing important insights into the protective effects of tripeptide NCW on hypertension.

Identification and molecular docking of tyrosinase inhibitory peptides from allophycocyanin in Spirulina platensis.

BACKGROUND: Tyrosinase, a copper-containing metalloenzyme with catalytic activity, is widely found in mammals. It is the key rate-limiting enzyme that catalyzes melanin synthesis. For humans, tyrosinase is beneficial to the darkening of eyes and hair. However, excessive deposition of melanin in the skin can lead to dull skin color and lead to pigmentation. Therefore, many skin-whitening compounds have been developed to decrease tyrosinase activity. This study aimed to identify a new tyrosinase inhibitory peptide through enzymatic hydrolysis, in vitro activity verification, molecular docking, and molecular dynamics (MD) simulation. RESULTS: A tripeptide Asp-Glu-Arg (DER) was identified, with a '-CDOCKER_Energy' value of 121.26 Kcal mol-1 . DER has effective tyrosinase inhibitory activity. Research shows that its half maximal inhibitory concentration value is 1.04 ± 0.01 mmol L-1 . In addition, DER binds to tyrosinase residues His85, His244, His259, and Asn260, which are key residues that drive the interaction between the peptide and tyrosinase. Finally, through MD simulation, the conformational changes and structural stability of the complexes were further explored to verify and supplement the results of molecular docking. CONCLUSION: This experiment shows that DER can effectively inhibit tyrosinase activity. His244, His259, His260, and Asn260 are the critical residues that drive the interaction between the peptide and tyrosinase, and hydrogen bonding is an important force. DER from Spirulina has the potential to develop functional products with tyrosinase inhibition. © 2024 Society of Chemical Industry.

Interaction mechanism of egg derived peptides RVPSL and QIGLF with dipalmitoyl phosphatidylcholine membrane: microcalorimetric and molecular dynamics simulation studies.

BACKGROUND: Egg-derived peptides are becoming increasingly popular due to their biological activity and non-toxic effects. The egg-derived peptides Arg-Val-Pro-Ser-Leu (RVPSL) and Gln-Ile-Gly-Leu-Phe (QIGLF) display strong angiotensin-converting enzyme inhibitory activity and they can be taken up by intestinal epithelial cells. The interaction of the egg-derived peptides RVPSL and QIGLF with the membrane remains unclear. RESULTS: The position and structure of the peptides in the membrane were calculated. The maximum density values of RVPSL and QIGLF were 2.27 and 1.22 nm from the center of the 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membrane, respectively, indicating that peptides penetrated the membrane-water interface and were embedded in the membrane. The interaction of RVPSL and QIGLF with the DPPC membrane did not affect the average area per lipid or the lipid sequence parameters. The thermodynamic parameters ΔH, ΔG, and ΔS of the interaction between the peptide RVPSL with the DPPC membrane were 17.91 kJ mol-1 , -17.63 kJ mol-1 , 187.5 J mol-1 ·k-1 , respectively. The thermodynamic parameters ΔH, ΔG, and ΔS of the interaction between peptide QIGLF with DPPC membrane were 17.10 kJ mol-1 , -17.12 kJ mol-1 , 114.8 J mol-1 ·k-1 , respectively. CONCLUSION: The results indicated that the binding of peptides RVPSL and QIGLF to DPPC is an endothermic, spontaneous, and entropy-driven reaction. The results of the study are relevant to the problem of the low bioavailability of bioactive peptides (BP). © 2023 Society of Chemical Industry.

Identification and Molecular Mechanism of Novel Immunomodulatory Peptides from Gelatin Hydrolysates: Molecular Docking, Dynamic Simulation, and Cell Experiments.

The purpose of this study was to identify donkey-hide gelatin-derived immunomodulatory peptides targeting Toll-like receptor 4-myeloid differentiation 2 (TLR4-MD2) and elucidate their binding modes using physicochemical property prediction, molecular docking, molecular dynamics simulations, and in vitro cell experiments. After hydrolyzing gelatin, 519 peptides were identified by liquid chromatography-tandem mass spectrometry. Peptides VQLSGEEK and GFSGLDGAKG bound to TLR4-MD2 with high binding affinity. In TLR4-MD2, Arg90, Ser118, Phe126, Tyr131, and Arg264 were key residues involved in the binding of these peptides. The RMSD and Rg values demonstrated that VQLSGEEK-TLR4-MD2 and GFSGLDGAKG-TLR4-MD2 complexes had stable and compact conformations. VQLSGEEK and GFSGLDGAKG were found to increase the cell viability and phagocytic activity of RAW264.7 macrophages; significantly promote the production of cytokines TNF-α, IL-1ß, and IL-6 in cells; and inhibit the overproduction of nitric oxide (NO) and cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results provided preliminary evidence that VQLSGEEK and GFSGLDGAKG could function as two-way immunomodulatory peptides with immunostimulatory and anti-inflammatory activities.

Dissecting the potential mechanism of antihypertensive effects of RVPSL on spontaneously hypertensive rats via widely targeted kidney metabolomics.

BACKGROUND: Our previous study has demonstrated that the egg-white-derived peptide RVPSL can lower blood pressure in spontaneously hypertensive rats (SHRs), but its potential action mechanism remains unclear. In this work, the underlying mechanism of the antihypertensive effects of RVPSL in SHRs was elucidated using the widely targeted kidney metabolomics approach. RESULTS: Ten SHRs were divided into two groups: SHR-Untreated group (0.9% saline) and SHR-RVPSL group (50 mg kg-1 body weight RVPSL) for 4 weeks. After 4 weeks, kidney samples were collected and widely targeted (liquid chromatography-electrospray ionization-tandem mass spectrometry) metabolomics was used to detect metabolites. Fifty-six biomarkers were identified that may be associated with hypertension. Among them, 17 biomarkers were upregulated and 39 biomarkers were downregulated. The results suggested that eight potential biomarkers were identified in kidney samples: O-phospho-l-serine, tyramine, citric acid, 3-hydroxybutyrate, O-acetyl-l-serine, 15-oxo-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-oxoETE), dopaquinone and 3,3',5-triiodo-l-thyronine. These potential biomarkers mainly involved carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. CONCLUSION: The study suggested that RVPSL may exert antihypertensive effects through upregulation of O-phospho-l-serine, 3-hydroxybutyrate and 15-oxoETE, and downregulation of tyramine, citric acid, O-acetyl-l-serine, 3,3',5-triiodo-l-thyronine and dopaquinone. The antihypertensive effects of RVPSL may be related to carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. RVPSL exhibited a potent antihypertensive effect, and the antihypertensive effects were associated with inhibition of vascular smooth muscle cell proliferation, vascular remodeling, vascular endothelium dysfunction, restoring reactive oxygen species, oxidative stress, inflammation and immune reaction. © 2022 Society of Chemical Industry.

Transcriptomic Analysis of Human Keratinocytes Treated with Galactomyces Ferment Filtrate, a Beneficial Cosmetic Ingredient.

Galactomyces ferment filtrate (GFF, Pitera™) is a cosmetic ingredient known to have multiple skin care benefits, such as reducing redness and pore size via the topical application of its moisturizer form. Although GFF is known to act partly as an antioxidative agonist for the aryl hydrocarbon receptor (AHR), its significance in keratinocyte biology is not fully understood. In this study, we conducted a transcriptomic analysis of GFF-treated human keratinocytes. Three different lots of GFF consistently modulated 99 (22 upregulated and 77 downregulated) genes, including upregulating cytochrome P450 1A1 (CYP1A1), a specific downstream gene for AHR activation. GFF also enhanced the expression of epidermal differentiation/barrier-related genes, such as small proline-rich proteins 1A and 1B (SPRR1A and SPRR1B), as well as wound healing-related genes such as serpin B2 (SERPINB2). Genes encoding components of tight junctions claudin-1 (CLDN1) and claudin-4 (CLDN4) were also target genes upregulated in the GFF-treated keratinocytes. In contrast, the three lots of GFF consistently downregulated the expression of inflammation-related genes such as chemokine (C-X-C motif) ligand 14 (CXCL14) and interleukin-6 receptor (IL6R). These results highlight the beneficial properties of GFF in maintaining keratinocyte homeostasis.

Potential antihypertensive mechanism of egg white-derived peptide QIGLF revealed by proteomic analysis.

Previous work has shown that egg white-derived peptide QIGLF has significant in vivo antihypertensive activity. This study aimed to clarify the antihypertensive mechanisms of QIGLF on spontaneously hypertensive rats (SHRs) by a serum proteomic approach. Here, the tandem mass tag (TMT) quantitative proteomic was performed to discover serum protein changes in SHRs with QIGLF. As a result, SHRs with 4 weeks of QIGLF treatment have distinct serum protein expression profiles by principal component and Pearson's correlation coefficient analysis. Based on Gene Ontology (GO) annotation, oxygen transport and organelle fusion were found to be a regulated major biological process. Besides, aldosterone regulated sodium reabsorption, mitophagy, gap junction, and tight junction were significantly regulated based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. QIGLF might exert antihypertensive effects in the SHRs by inhibiting Na+ reabsorption and oxidative stress, restoring gap junction and tight junction.

Interaction mechanism of three egg protein derived ACE inhibitory tri-peptides and DPPC membrane using FS, FTIR, and DSC studies.

Understanding the interaction of food derived angiotensin converting enzyme (ACE) inhibitory peptides and intestinal epithelial cell membrane may help to improve their absorption. This research aimed to study the molecular interaction of ACE inhibitory tri-peptides ADF, FGR, and MIR with DPPC membrane during absorption process. The DPPC liposome was prepared and characterized, then used as a model membrane. The permeability of tri-peptides across the membrane was investigated using Fluorescence spectroscopy. The effect of tri-peptides on the structure and dynamics of DPPC bilayers was determined using Fourier transform infrared spectroscopy. The effect of tri-peptides on the phase transition temperature in the DPPC membrane was also analyzed using Differential scanning calorimetry. The results showed that ACE inhibitory tri-peptides ADF, FGR, and MIR can penetrate into both the membrane-water interface and hydrophobic region of DPPC bilayer, and the tri-peptide FGR have higher permeability across the membrane.

A Potential Role of Keratinocyte-Derived Bilirubin in Human Skin Yellowness and Its Amelioration by Sucrose Laurate/Dilaurate.

Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone. Bilirubin is a yellow chromophore known to be made in the liver and/or spleen and is transported throughout the body via the blood stream. Recent publications suggest bilirubin may be synthesized in other cells/organs, including the skin. We found human keratinocytes express the transcripts involved in bilirubin biosynthesis. In parallel, we also found human keratinocytes could indeed synthesize bilirubin in monolayer keratinocytes and in a 3D human skin-equivalent model. The synthesized amount was substantial enough to contribute to skin yellowness. In addition, oxidative stress enhanced bilirubin production. Using UnaG, a protein that forms a fluorescent species upon binding to bilirubin, we also visualized the intracellular expression of bilirubin in keratinocytes. Finally, we screened a compound library and discovered that the sucrose laurate/dilaurate (SDL) combination significantly reduced bilirubin levels, as well as bilirubin-mediated yellowness. In conclusion, bilirubin is indeed synthesized in epidermal keratinocytes and can be upregulated by oxidative stress, which could contribute to chronic or transient yellow skin tone appearance. Application of SDL diminishes bilirubin generation and may be a potential solution to mitigate yellowish and/or dull skin appearance.

Underlying antihypertensive mechanism of egg white-derived peptide QIGLF using renal metabolomics analysis.

The kidney is an important target organ in the treatment of hypertension, but the effect of peptide QIGLF with antihypertensive activity on kidneys remains unknown. In the work, we aimed to further understand the hypotensive effects of QIGLF in spontaneously hypertensive rats (SHRs) using widely targeted metabolomics technology to investigate the kidney metabolic profiling variations. After four weeks of oral administration, the results showed different renal metabolomics profiles between QIGLF and model groups. Besides, a total of 10 potential biomarkers were identified, that is, 3-hydroxybutanoate, 20-hydroxyeicosatetraenoic acid, 19(S)-hydroxyeicosatetraenoic acid, 15-oxoETE, L-ornithine, malonate, uridine, uridine 5'-monophosphate, argininosuccinic acid, and N-carbamoyl-L-aspartate. These metabolites might exhibit antihypertensive activity of QIGLF by regulating synthesis and degradation of ketone bodies, arachidonic acid metabolism, pyrimidine metabolism, and arginine biosynthesis. These findings suggest that QIGLF might alleviate hypertension by inhibiting renal inflammation, promoting natriuresis, and regulating renal nitric oxide production.

Identification and molecular mechanism of novel tyrosinase inhibitory peptides from collagen.

This study aimed to identify novel tyrosinase inhibitory peptides from collagen of donkey by combining in silico screening with in vitro activity verification, and to elucidate inhibition mechanism based on molecular docking and molecular dynamics simulation. Three tripeptides, that is, Asp-Gly-Leu (DGL), Gly-Ala-Arg (GAR), and Ser-Asp-Trp (SDW) were identified and exerted potent tyrosinase inhibitory activities, with IC50 values of 0.47 ± 0.01 mM, 1.13 ± 0.04 mM, and 2.08 ± 0.01 mM, respectively. Each of three identified peptides had hydrophobic amino acids and could stably and closely bind with the active pocket of tyrosinase. Hydrogen bonds played the most important roles in impacting the structure stabilities of the peptide-tyrosinase complexes. Moreover, His85, His244, His259, and Asn260 were the key residues to drive the interactions between the peptides and tyrosinase. Overall, collagen-derived peptides DGL, GAR, and SDW from donkey had great potential as tyrosinase inhibitory peptides. PRACTICAL APPLICATION: This study has suggested that three tripeptides DGL, GAR, and SDW derived from collagen of donkey have potent tyrosinase inhibitory activity. These novel collagen-derived peptides had great potential to be applied as tyrosinase inhibitory peptides to prevent and improve hyperpigmentation disorders and other tyrosinase-related problems in the food industry. And this work is expected to provide a theoretical basis for the development of novel, safe, and effective tyrosinase inhibitory peptides.

Antihypertensive effect and underlying mechanism of tripeptide NCW on spontaneously hypertensive rats using metabolomics analysis.

Tripeptide NCW identified in our previous study displayed a strong ACE inhibitory activity, but whether it has any antihypertensive effect in vivo remains unknown. Thus, in this study, we aimed to investigate the protective effects of tripeptide NCW in spontaneously hypertensive rats (SHRs) and to further figure out the serum metabolic profiling variations due to its oral administration via UPLC-Q-TOF-MS/MS-based metabolomics analysis to clarify the underlying hypotensive mechanism. After three weeks of oral administration, the tripeptide NCW-treated group (NCW/SHR group, 80 mg per kg BW per d) showed significantly reduced systolic and diastolic blood pressure by 48.08 ± 3.84 mmHg and 48.92 ± 5.77 mmHg, respectively. Additionally, a total of 25 blood pressure-related metabolites were identified as being significantly changed in SHRs given tripeptide NCW after three weeks. These 25 metabolites might be biomarkers that indicated that the tripeptide NCW exhibits antihypertensive activity via regulating bile acid metabolism, lipid metabolism, amino acid metabolism, purinergic signaling, pantothenate and CoA biosynthesis, and the citrate cycle. Collectively, tripeptide NCW has a protective effect on SHRs associated with serum metabolite abnormalities.

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2.

COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (Mpro), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were predicted using various online tools. The molecular interactions between Mpro and the peptides were studied using molecular docking and molecular dynamic simulation. The results demonstrated that peptide GSRY was predicted to have better physicochemical properties, and the value of '-C DOCKER interaction energy' between peptide GSRY and Mpro was 80.8505 kcal/mol. The interaction between the peptide GSRY and the native ligand N3 co-crystallized with Mpro had overlapped amino acids, i.e., HIS163, GlY143, GLU166, GLN189 and MET165. Molecular dynamic simulation revealed that Mpro/GSRY complexes were stable. Collectively, the peptide GSRY may be a potential candidate drug against Mpro of SARS-CoV-2.

Identification of Oncorhynchus mykiss nebulin-derived peptides as bitter taste receptor TAS2R14 blockers by in silico screening and molecular docking.

Human bitter taste receptor TAS2R14 (T2R14) can widely perceive bitterness, which has always been an issue for people to overcome. This study was aimed at identifying bioactive peptides obtained from Oncorhynchus mykiss nebulin hydrolysates as bitter taste receptor blockers by physicochemical property prediction, molecular docking, and in vitro determination of bitterness intensity using electronic tongue. Exploration of the interaction mechanism of these peptides with T2R14 by molecular docking models indicated that peptides ADM and ADW had high affinities for T2R14 to block the binding of bitter substances into the receptor. Addition of ADM and ADW to quinine caused reduction in bitterness intensity, with IC50 values of 420.32 ± 6.26 µM and 403.29 ± 4.10 µM, respectively. Hydrogen bond interaction and hydrophobic interaction were responsible for manifesting the high affinities of these peptides for the receptor. Residues Thr86, Asp168, and Phe247 may be the key amino acids within the binding site.

Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment.

Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment. In addition, in order to understand the effect that multiple fractional laser treatments have on skin rejuvenation, several sites were treated sequentially with either 1, 2, 3, or 4 treatments (with 28 days between treatments) followed by the collection of 4 mm punch biopsies. RNA was extracted from the biopsies, analyzed using Affymetrix U219 chips and gene expression was compared between untreated and treated sites. We observed dramatic changes in gene expression as early as 1 day after fractional laser treatment with changes remaining elevated even after 1 month. Analysis of individual genes demonstrated significant and time related changes in inflammatory, epidermal, and dermal genes, with dermal genes linked to extracellular matrix formation changing at later time points following fractional laser treatment. When comparing the age-related changes in skin gene expression to those induced by fractional laser, it was observed that fractional laser treatment reverses many of the changes in the aging gene expression. Finally, multiple fractional laser treatments, which cover different regions of a treatment area, resulted in a sustained or increased dermal remodeling response, with many genes either differentially regulated or continuously upregulated, supporting previous observations that maximal skin rejuvenation requires multiple fractional laser treatments. In conclusion, fractional laser treatment of human skin activates a number of biological processes involved in wound healing and tissue regeneration.

Identification and molecular docking of peptides from Mizuhopecten yessoensis myosin as human bitter taste receptor T2R14 blockers.

Bitter taste receptor 14(T2R14) is one of the most widely regulated bitter taste receptors (T2Rs) and plays a vital role in the research of T2R blockers. In this study, potential T2R14 blockers were identified from the myosin of Mizuhopecten yessoensis. Myosin was hydrolyzed in silico by gastrointestinal proteases, and the peptides were obtained. The peptides' biological activity, solubility, and toxicity were predicted, and the potential T2R14 blocking peptides were docked with T2R14. Subsequently, the in vitro T2R14 blocking activity of the selected peptide was verified by an electronic tongue. The results showed that QRPR had T2R14 blocking activity with an IC50 value of 256.69 ± 1.91 µM. Molecular docking analysis suggested the key role of the amino residues Asp168, Leu178, Asn157, and Ile262 in blocking T2R14, and revealed that the amino acid residues of T2R14 bound with the peptide QRPR via electrostatic interaction, hydrophobic interaction, conventional hydrogen bond, and hydrogen bond. The novel T2R14 blocking peptide QRPR is a potential candidate for suppressing bitterness.

Identification of nut protein-derived peptides against SARS-CoV-2 spike protein and main protease.

Recently, an outbreak of a novel coronavirus disease (COVID-19) has reached pandemic proportions, and there is an urgent need to develop nutritional supplements to assist with prevention, treatment, and recovery. In this study, SARS-CoV-2 inhibitory peptides were screened from nut proteins in silico, and binding affinities of the peptides to the SARS-CoV-2 main protease (Mpro) and the spike protein receptor-binding domain (RBD) were evaluated. Peptide NDQF from peanuts and peptide ASGCGDC from almonds were found to have a strong binding affinity for both targets of the coronavirus. The binding sites of the NDQF and ASGCGDC peptides are highly consistent with the Mpro inhibitor N3. In addition, NDQF and ASGCGDC exhibited an effective binding affinity for amino acid residues Tyr453 and Gln493 of the spike RBD. Molecular dynamics simulation further confirmed that the NDQF and ASGCGDC peptides could bind stably to the SARS-COV-2 Mpro and spike RBD. In summary, nut protein may be helpful as nutritional supplements for COVID-19 patients, and the screened peptides could be considered a potential lead compound for designing entry inhibitors against SARS-CoV-2.

Potential Antihypertensive Mechanisms of the Egg White-Derived Peptide QIGLF in Spontaneously Hypertensive Rats Revealed Using Untargeted Serum Metabolomics.

The angiotensin-converting enzyme (ACE) inhibitory peptide QIGLF derived from egg white was shown to have significant in vivo antihypertensive effects in our previous study, but the intervention mechanisms at the metabolic level are still unclear. The UPLC-QTOF/MS-based untargeted metabolomics approach was used to clarify the potential antihypertensive mechanisms of QIGLF in the serum of spontaneously hypertensive rats (SHRs). Multivariate statistical analysis showed a clear difference in the metabolite profiles between the QIGLF and model groups. The results suggested that eight potential biomarkers were identified, that is, adrenic acid, ursodeoxycholic acid, glycocholic acid, taurocholic acid, tryptophan, acetylindoxyl, tyrosine, and 2-phenylethanol, which were mainly involved in aromatic amino acid biosynthesis and metabolism, biosynthesis of bile acid, and biosynthesis of unsaturated fatty acids. QIGLF might exert antihypertensive effects by improving endothelial dysfunction. This study provides a theoretical basis for future research and application of ACE inhibitory peptides in the prevention and improvement of hypertension.

Potential mechanisms of the anti-hypertensive effects of RVPSL on spontaneously hypertensive rats using non-targeted serum metabolomics.

The study aimed to investigate potential mechanisms for the anti-hypertensive effects of RVPSL on spontaneously hypertensive rats (SHRs) using a non-targeted metabonomic approach. In this study, UPLC/MS-based non-targeted metabolomics was performed to discover metabolite variation of serum in SHRs with RVPSL treatment. As a result, the serum metabolites of SHRs that were administered RVPSL for four weeks exhibited distinct alterations. Nine potential biomarkers, i.e., choline, adenosine, adrenic acid, L-tryptophan, niacinamide, glycocholic acid, propiolic acid, D-glyceraldehyde 3-phosphate, and phosphoglycolic acid, were significantly altered, which were mainly involved in lipid metabolism, vitamin and amino acid metabolism, purine metabolism, the MAPK signaling pathway, and the renin-angiotensin system. This study suggested that RVPSL potentially exerted potent effects of alleviating hypertension in the SHRs mainly via integrated regulations of metabolism and production of choline, L-tryptophan, nicotinamide, and adenosine.