Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.

Screening of inhibitors on successful covalent tyrosinase coupling with help from SpyBank.

Microbial metabolites are an important source of tyrosinase (TYR) inhibitors because of their rich chemical diversity. However, because of the complex metabolic environment of microbial products, it is difficult to rapidly locate and identify natural TYR inhibitors. Affinity-based ligand screening is an important method for capturing active ingredients in complex samples, but ligand immobilization is an important factor affecting the screening process. In this paper, TYR was used as ligand, and the SpyTag/SpyCatcher coupling system was used to rapidly construct affinity chromatography vectors for screening TYR inhibitors and separating active components from complex samples. We successfully expressed SpyTag-TYR fusion protein and SpyCatcher protein, and incubated SpyCatcher protein with epoxy-activated agarose. The SpyTag-TYR protein was spontaneously coupled with SpyCatcher to obtain an affinity chromatography filler for immobilization of TYR, and the performance of the packaging material was characterized. Finally, compound 1 with enzyme inhibitory activity was successfully obtained from the fermentation product of marine microorganism C. Through HPLC, MS, 1H NMR and 13C NMR analyses, its structure was deduced as azelaic acid, and its activity was analyzed. The results showed that this is a feasible method for screening TYR inhibitors in complex systems.

Hair Follicle-Targeted Delivery of Azelaic Acid Micro/Nanocrystals Promote the Treatment of Acne Vulgaris.

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.

Novel antiarthritic mechanisms of Azelaic acid against CFA-induced arthritis in rats by modulating pro- and anti-inflammatory cytokines network.

An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund's Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1ß, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1ß, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA.

A randomized controlled double-blinded split-face prospective clinical trial to assess the efficacy, safety, and tolerability of a novel 3-step routine compared to benzoyl peroxide for the treatment of mild to moderate acne vulgaris.

Adult acne vulgaris affects up to 43-51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. "I would use this in the future) and performance ("my skin improved" and "helped my acne clear up faster"). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris.

Effects of 15% Azelaic Acid Gel in the Management of Post-Inflammatory Erythema and Post-Inflammatory Hyperpigmentation in Acne Vulgaris.

INTRODUCTION: The aim of this study was to assess the efficacy and safety of 15% azelaic acid (AzA) gel in treating acne-induced post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH). The effects of 15% AzA gel on acne, skin barrier function, and quality of life were also evaluated. METHODS: A total of 72 patients with mild to moderate acne were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were divided into two groups: patients in the AzA group applied 15% AzA gel twice daily for 12 weeks, and those in the placebo group applied AzA-free gel. Clinical evaluations using non-invasive skin detection technologies, including VISIA skin analysis, dermoscopy, and skin physiological function tests, were performed at 0, 4, 8, and 12 weeks. Main outcome measures included the post-acne hyperpigmentation index (PAHPI), melanin, hemoglobin, individual typology angle, water content, transepidermal water loss, and sebum. Investigator Global Assessment) and Dermatology Life Quality Index (DLQI) assessments were conducted at weeks 0 and 12. Adverse reactions were recorded. RESULTS: Of the 72 patients at study initiation, 60 completed the trial. At 8 and 12 weeks, patients in the AzA group showed significantly reduced PAHPI for PIE lesions compared to baseline and patients receiving placebo (P < 0.05). Patients in both groups exhibited reduced PIH lesions at weeks 8 and 12 that differed significantly from baseline (P < 0.05). Hemoglobin content decreased significantly in AzA-treated PIE lesions compared to those treated with placebo at week 12 (P < 0.05). Melanin content decreased significantly in AzA-treated PIH lesions at week 12 (P < 0.05). The AzA group showed higher improvement in DLQI (P < 0.05), and greater overall satisfaction (P < 0.05) compared to placebo. CONCLUSION: The results indicate that 15% AzA gel effectively improved acne-induced PIE and PIH with minimal adverse reactions, making it a viable clinical application. In the study population, it had no adverse effects on skin barrier function and contributed positively to acne improvement and patient quality of life. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (ChiCTR.org.cn) under the identifier ChiCTR2300076959. The registration date was 25 October 2023, retrospectively registered.

Lipid peroxidation and stress-induced signalling molecules in systemic resistance mediated by azelaic acid/AZELAIC ACID INDUCED1: signal initiation and propagation.

Systemic acquired resistance protects plants against a broad spectrum of secondary infections by pathogens. A crucial compound involved in the systemic spread of the threat information after primary pathogen infection is the C9 oxylipin azelaic acid (AZA), a breakdown product of unsaturated C18 fatty acids. AZA is generated during lipid peroxidation in the plastids and accumulates in response to various abiotic and biotic stresses. AZA stimulates the expression of AZELAIC ACID INDUCED1 (AZI1), and a pool of AZI1 accumulates in the plastid envelope in association with AZA. AZA and AZI1 utilize the symplastic pathway to travel through the plasmodesmata to neighbouring cells to induce systemic stress resistance responses in distal tissues. Here, we describe the synthesis, travel and function of AZA and AZI1 and discuss open questions of signal initiation and propagation.

Structural elucidation and development of azelaic acid loaded mesoporous silica nanoparticles infused gel: Revolutionizing nanodrug delivery for cosmetics and pharmaceuticals.

This research aimed to enhance dermal delivery and optimize depigmentation therapy by designing mesoporous silica nanoparticles (MSNs) encapsulating azelaic acid (AZA) within a gel matrix. The MSNs were prepared using the sol-gel method. After subsequent processes, including acid extraction and drug loading, were then elucidated through PDI, size, zeta-potential, entrapment efficiency, nitrogen adsorption assay, FE-SEM, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and tyrosinase inhibition assay, were employed to assess the formulation. In-vitro stability tests for both AZA-MSN gel (AZCG) and AZA-loaded mesoporous silica gel (AZMG) were conducted at 8 °C, 25 °C, 40 °C, and 40 °C + 75 % RH, encompassing assessments of color, liquefaction, pH, and conductivity. Our findings showed a notable entrapment efficiency of 93.46 % for AZA-MSNs, with FE-SEM illustrating porous spherical MSNs. The particle size of AZA-MSNs was determined to be 211.9 nm, with a pore size of 2.47 nm and XRD analysis confirmed the amorphous state of AZA within the MSN carriers. Rheology examination indicated a non-Newtonian flow, while ex-vivo rat skin permeation studies conducted in a phosphate buffer (pH = 5.5) demonstrated a biphasic release pattern with 85.53 % cumulative drug permeation for AZA-MSNs. Overall, the study endorse the potential of AZA-MSNs as an efficacious and stable formulation for AZA delivery, highlighting their promise in addressing pigmentation concerns compared to conventional approaches.

Ozonated Sunflower Oil Embedded within Spray-Dried Chitosan Microspheres Cross-Linked with Azelaic Acid as a Multicomponent Solid Form for Broad-Spectrum and Long-Lasting Antimicrobial Activity.

Multicomponent solid forms for the combined delivery of antimicrobials can improve formulation performance, especially for poorly soluble drugs, by enabling the modified release of the active ingredients to better meet therapeutic needs. Chitosan microspheres incorporating ozonated sunflower oil were prepared by a spray-drying method and using azelaic acid as a biocompatible cross-linker to improve the long time frame. Two methods were used to incorporate ozonated oil into microspheres during the atomization process: one based on the use of a surfactant to emulsify the oil and another using mesoporous silica as an oil absorbent. The encapsulation efficiency of the ozonated oil was evaluated by measuring the peroxide value in the microspheres, which showed an efficiency of 75.5-82.1%. The morphological aspects; particle size distribution; zeta potential; swelling; degradation time; and thermal, crystallographic and spectroscopic properties of the microspheres were analyzed. Azelaic acid release and peroxide formation over time were followed in in vitro analyses, which showed that ozonated oil embedded within chitosan microspheres cross-linked with azelaic acid is a valid system to obtain a sustained release of antimicrobials. In vitro tests showed that the microspheres exhibit synergistic antimicrobial activity against P. aeruginosa, E. coli, S. aureus, C. albicans and A. brasiliensis. This makes them ideal for use in the development of biomedical devices that require broad-spectrum and prolonged antimicrobial activity.

755-nm picosecond laser plus topical 20% azelaic acid compared to topical 20% azelaic acid alone for the treatment of melasma: a randomized, split-face and controlled trial.

PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

Azelaic acid can efficiently compete for the auxin binding site TIR1, altering auxin polar transport, gravitropic response, and root growth and architecture in Arabidopsisthaliana roots.

The present study investigates the phytotoxic potential of azelaic acid (AZA) on Arabidopsis thaliana roots. Effects on root morphology, anatomy, auxin content and transport, gravitropic response and molecular docking were analysed. AZA inhibited root growth, stimulated lateral and adventitious roots, and altered the root apical meristem by reducing meristem cell number, length and width. The treatment also slowed down the roots' gravitropic response, likely due to a reduction in statoliths, starch-rich organelles involved in gravity perception. In addition, auxin content, transport and distribution, together with PIN proteins' expression and localisation were altered after AZA treatment, inducing a reduction in auxin transport and its distribution into the meristematic zone. Computational simulations showed that AZA has a high affinity for the auxin receptor TIR1, competing with auxin for the binding site. The AZA binding with TIR1 could interfere with the normal functioning of the TIR1/AFB complex, disrupting the ubiquitin E3 ligase complex and leading to alterations in the response of the plant, which could perceive AZA as an exogenous auxin. Our results suggest that AZA mode of action could involve the modulation of auxin-related processes in Arabidopsis roots. Understanding such mechanisms could lead to find environmentally friendly alternatives to synthetic herbicides.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid.

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a 'C4-TRAP transporter', and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10-9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 µM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

The multiple uses of azelaic acid in dermatology: mechanism of action, preparations, and potential therapeutic applications.

Azelaic acid (AZA) is a naturally occurring saturated dicarboxylic acid whose topical application has found multiple uses in dermatology. Its anti-inflammatory, antioxidant and antimicrobial properties against Propionibacterium acne are currently used in the treatment of various types of acne such as rosacea and acne vulgaris. AZA is an inhibitor of tyrosinase, mitochondrial respiratory chain enzymes and DNA synthesis, and is a scavenger of harmful free radicals and inhibits the production of reactive oxygen species by neutrophils. Interestingly, AZA also has anti-proliferative and cytotoxic effects on various cancer cells. To date, its inhibitory effect on melanocytes has been mainly used, making it widely used in the treatment of hyperpigmentation disorders such as melasma and post-inflammatory hyperpigmentation. Commercially available topical formulations with cosmetic and drug status contain 5% to 20% AZA in the form of gels and creams. The use of liposomal technology allows greater control over the pharmacokinetics and pharmacodynamics of the formulations. When applied topically, AZA is well tolerated, and side effects are limited to generally mild and transient local skin irritation. Importantly, liposomal technology has enabled the drug to penetrate all layers of the skin while maintaining a very high accumulation of the active ingredient. This solution could be revolutionary for the treatment of skin cancer, where until now the main obstacle was poor absorption through the skin, making the treatment require multiple applications to maintain long-term activity levels. In this review, we will present the mechanism of action and pharmacokinetics of AZA. We will summarize its use in the treatment of dermatoses and its potential in skin cancer therapy. We will provide an overview of the preparations available on the market, taking into consideration technologies used.

Determination of azelaic acid and potassium azeloycinate diglycinate in cosmetics by HPLC / 上海预防医学

ObjectiveAn HPLC method was established for the determination of azelaic acid and potassium azeloycinate diglycinate in cosmetics. MethodsThe samples were extracted with 60 mmol·L-1 sodium hydroxide water solution-methyl alcohol. After centrifugation and filtration， the analysis of azelaic acid and potassium azeloycinate diglycinate was performed with a SVEA C8（250 mm×4.6 mm， 5 μm） column， using 15 mmol‧L-1 potassium dihydrogen phosphate solution （pH=3.0） and acetonitrile for gradient elution at a flow rate of 1.0 mL·min-1.The analytes were detected with UV detector， and quantified by external standard curve. ResultsThe results showed a good linearity in the range of 5‒1 000 μg‧mL-1 with correlation coefficients （r） larger than 0.999. The detection limit of azelaic acid and potassium azeloycinate diglycinate （LOD） was 0.020% and 0.015%， respectively. The spiked recoveries were 87.66% to 108.96% with the relative standard deviation （RSD） of 0.6% to 3.3%. ConclusionThe method is simple， rapid and highly sensitive. It is suitable for the determination of azelaic acid and potassium azeloycinate diglycinate in cosmetics.

Preliminary discovery of quality marker (Q-marker) of Shenzhiling Oral Liquid based on “fingerprint-efficacy-pharmacokinetics” correlation / 中草药

Objective: To establish a research strategy for discovering quality marker (Q-marker) of Shenzhiling Oral Liquid based on the “fingerprint-efficacy-pharmacokinetics” correlation. Methods: HPLC fingerprints and acetylcholinesterase (AchE) inhibitory activities of 12 batches of Shenzhiling Oral Liquid were analyzed. The correlation analysis between the HPLC fingerprints and AchE inhibitory effects were carried out with orthogonal signal correction-partial least squares regression (OSC-PLSR) method. Combined with network pharmacology, efficacy-related components were determined. By identifying the compounds absorbed and exposed in vivo, pharmacologically active components were determined. Finally, Q-marker could be preliminarily discovered by the comprehensive analysis associated with the integration of efficacy-related components and pharmacologically active ingredients. Results: The results of OSC-PLSR analysis showed that three efficacy-related components were closely related to AchE inhibitory activities. According to mapping the targets of diseases, 61 efficacy-related components were determined. Eleven active compounds in plasma were identified by UHPLC-quadrupole-orbitrap-MS. The Q-markers of Shenzhiling Oral Liquid were liquiritin apioside, albiflorin and azelaic acid preliminarily determined by integrated and comprehensive analysis. Conclusion: The combination of fingerprint-efficacy relationship, network pharmacology and components absorbed in plasma could be an effective way for rapid analysis and discovery of Q-marker in Shenzhiling Oral Liquid, which will be of great significance both to improve the quality control and evaluation, and ensure the safety and effectiveness of traditional Chinese medicines.

Chemical constituets of Sparganium stoloniferum / 中草药

Objective: To study the chemical constituents of Sparganium stoloniferum. Methods: Column chromatographic techniques were applied to isolate the constituents. The chemical structures of the constituents were elucidated on the basis of physicochemical properties and spectral data. Results: Twelve compounds were isolated and identified as β-sitosterol palmitate (1), β-sitosterol (2), azelaic acid (3), docosanoic acid (4), 6,7,10-trihydroxy-8-octadecenoic acid (5), p-hydroxybenzaldehyde (6), sanleng diphenyl-acetypene (7), ferulic acid (8), 3,5-dihydroxy-4-methoxy-benzoic acid (9), 2,7-dihydroxy-xanthone (10), glycerol ferulate (11), and daucosterol (12). Conclusion: Compounds 3,4, and 9-11 are obtained from the plants of Sparganium L. for the first time.