Comparative Analysis of Metabolite Profiling of Momordica charantia Leaf and the Anti-Obesity Effect through Regulating Lipid Metabolism.

This study investigated the effects of Momordica charantia (M. charantia) extract in obesity and abnormal lipid metabolism in mice fed high fat diet (HFD). Fruit, root, stem, and leaf extracts of M. charantia were obtained using distilled water, 70% ethanol and 95% hexane. M. charantia leaf distilled water extract (MCLW) showed the highest antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests and reducing power. Metabolite profiles of M. charantia leaf extracts were analyzed for identification of bioactive compounds. HFD-fed mice were treated with MCLW (oral dose of 200 mg/kg/d) for 4 weeks. MCLW reduced lipid accumulation, body weight, organ weight, and adipose tissue volume and significantly improved glucose tolerance and insulin resistance in HFD mice. Furthermore, MCLW administration reduced serum total cholesterol and low-density lipoprotein cholesterol, and increased serum high-density lipoprotein cholesterol compared with HFD mice. Moreover, MCLW significantly reduced the levels of serum urea nitrogen, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase; alleviated liver and kidney injury. MCLW decreases expression of genes that fatty acid synthesis; increase the expression of catabolic-related genes. These results indicate that MCLW has an inhibitory effect on obese induced by high fat diet intake, and the mechanism may be related to the regulation of abnormal lipid metabolism in liver and adipose tissue, suggesting that MCLW may be a suitable candidate for the treatment of obesity.

Protective Effects of Novel Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler Against Oxidative Stress in Chang Liver Cells in Vitro and in a Zebrafish Model In Vivo.

Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals.

The Role of Momordica charantia in Resisting Obesity.

Momordica charantia (M. charantia), commonly known as bitter gourd, bitter melon, kugua, balsam pear, or karela, is a tropical and sub-tropical vine belonging to the Cucurbitaceae family. It has been used to treat a variety of diseases in the traditional medicine of China, India, and Sri Lanka. Here, we review the anti-obesity effects of various bioactive components of M. charantia established at the cellular and organismal level. We aim to provide links between various bioactive components of M. charantia and their anti-obesity mechanism. An advanced search was conducted on the worldwide accepted scientific databases via electronic search (Google Scholar, Web of Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, SciFinder, CNKI) database with the query TS = "Momordica charantia" and "obesity". Information was also obtained from International Plant Names Index, Chinese Pharmacopoeia, Chinese herbal classic books, online databases, PhD and MSc dissertations, etc. First, studies showing the anti-obesity effects of M. charantia on the cells and on animals were classified. The major bioactive components that showed anti-obesity activities included proteins, triterpenoids, saponins, phenolics, and conjugated linolenic acids. Their mechanisms included inhibition of fat synthesis, promotion of glucose utilization, and stimulation of auxiliary lipid-lowering activity. Finally, we summarized the risks of excessive consumption of M. charantia and the application. Although further research is necessary to explore various issues, this review establishes the therapeutic potential of M. charantia and it is highly promising candidate for the development of anti-obesity health products and medicines.

Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice.

Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/µM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.

Immune-Stimulatory Effects of Althaea rosea Flower Extracts through the MAPK Signaling Pathway in RAW264.7 Cells.

Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF) extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO production and cytokines (IL-6 and TNF-α). We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of A. rosea flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α) and other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds.

Biosynthesis of Oligomeric Anthocyanins from Grape Skin Extracts.

We synthesized oligomeric anthocyanins from grape skin-derived monomeric anthocyanins such as anthocyanidin and proanthocyanidin by a fermentation technique using Aspergillus niger, crude enzymes and glucosidase. The biosyntheses of the oligomeric anthocyanins carried out by the conventional method using Aspergillus niger and crude enzymes were confirmed by ESI-MS. The molecular weight of the synthesized anthocyanin oligomers was determined using MALDI-MS. The yield of anthocyanin oligomers using crude enzymes was higher than that of the synthesis using Aspergillus fermentation. Several studies have been demonstrated that oligomeric anthocyanins have higher antioxidant activity than monomeric anthocyanins. Fermentation-based synthesis of oligomeric anthocyanins is an alternative way of producing useful anthocyanins that could support the food industry.

Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance.

BACKGROUND: Moringa oleifera (M. oleifera) is widely cultivated in tropical and subtropical regions and has been used as a vegetable and in traditional medicine. In this study, the anti-atopic dermatitis activity of the ethanol extract of M. oleifera leaf was investigated in vitro and in vivo. METHODS: For the in vitro study, HaCaT human keratinocytes were used for cytokines and MAPKinase assay. In the in vivo study, M. oleifera leaf ethanolic extract (MO) was topically applied to BALB/c mice with Dermatophagoides farinae extract (DFE; house dust mite extract)- and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). RESULTS: The expression of TNF-α, CCL17, IL-1ß, IL-6 pro-inflammatory cytokine-related mRNA, and mitogen-activated protein kinases (MAPKs) in TNF-α/IFN-γ-induced HaCaT keratinocytes were reduced by MO. Epidermal and dermal ear thickness, mast cell infiltration, serum immunoglobulin levels, as well as gene expression of various cytokines in the ear tissue, lymph nodes, and splenocytes were improved by treatment with MO. In addition, MO reduced the expression of retinoic acid-related orphan receptor γT (RORγT), thymic stromal lymphopoietin (TSLP), and mannose receptor (CD206) mRNA in the ear tissue and improved cervical lymph node size. CONCLUSION: The results of this study strongly suggest the beneficial effects of MO on AD via the regulation of inflammatory responses.

Antioxidant and Anti-Inflammatory Effects of Chaenomeles sinensis Leaf Extracts on LPS-Stimulated RAW 264.7 Cells.

The fruit of Chaenomeles sinensis has been traditionally used in ethnomedicine for the treatment of various human ailments, including pneumonia, bronchitis, and so on, but the pharmacological applications of the leaf part of the plant have not been studied. In this study, we evaluated the various radical scavenging activities and anti-inflammatory effects of different Chaenomeles sinensis leaf (CSL) extracts. The water extract showed a higher antioxidant and radical scavenging activities. However the ethanolic extracts showed higher NO scavenging activity than water extract, therefore the ethanolic extract of CSL was examined for anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The 70% ethanol extract of CSL (CSLE) has higher anti-inflammatory activity and significantly inhibited the production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, CSLE suppressed LPS-stimulated inducible nitric oxide synthase (iNOS) and NO production, IL-1ß and phospho-STAT1 expression. In this study, we investigated the effect of CSLE on the production of inflammatory mediators through the inhibition of the TRIF-dependent pathways. Furthermore, we evaluated the role of CSLE on LPS-induced expression of pro-inflammatory cytokines, such as TNF-α, IL-1ß and IL-6. Our results suggest that CSLE attenuates the LPS-stimulated inflammatory responses in macrophages through regulating the key inflammatory mechanisms, providing scientific support for its traditional uses in treating various inflammatory diseases.

Characterization of the antioxidant fraction of Trapa japonica pericarp and its hepatic protective effects in vitro and in vivo.

The ethanolic extract of Trapa japonica pericarp (TJP) and its various fractions were evaluated for their antioxidant potential. The ethyl acetate fraction (EF) from TJP exhibited significant antioxidant and protective effects against tert-butylhydroperoxide (t-BHP)-induced oxidative damage in vitro and in vivo. In vitro experimental results showed that the EF suppressed t-BHP-induced damage in Chang cells by inhibiting reactive oxygen species generation and regulating the mitochondrial membrane potential. Furthermore, western blot analysis showed that the EF effectively inhibited t-BHP-induced apoptosis by suppressing caspase-3, caspase-7, caspase-8, and caspase-9. In the in vivo study, the EF significantly prevented serum increases in glutamate oxaloacetate transaminase and glutamate pyruvate transaminase and hepatic malondialdehyde levels caused by t-BHP. Furthermore, the EF markedly increased hepatic superoxide dismutase, catalase, and glutathione levels. Histopathological examinations further confirmed that the EF could protect the liver from t-BHP-induced oxidative injury. These findings indicate that the EF could be developed as a therapy or to prevent hepatic injury.

Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells.

Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

6,6'-Bieckol protects insulinoma cells against high glucose-induced glucotoxicity by reducing oxidative stress and apoptosis.

Pancreatic ß cells are highly sensitive to oxidative stress, which might play an important role in ß cell death in diabetes. The protective effect of 6,6'-bieckol, a phlorotannin polyphenol compound purified from Ecklonia cava, against high glucose-induced glucotoxicity was investigated in rat insulinoma cells. High glucose (30 mM) treatment induced the death of rat insulinoma cells, but treatment with 10 or 50 µg/mL 6,6'-bieckol significantly inhibited the high glucose-induced glucotoxicity. Furthermore, treatment with 6,6'-bieckol dose-dependently reduced the level of thiobarbituric acid reactive substances, generation of intracellular reactive oxygen species, and the level of nitric oxide, all of which were increased by high glucose concentration. In addition, 6,6'-bieckol protected rat insulinoma cells from apoptosis under high-glucose conditions. These effects were associated with increased expression of the anti-apoptotic protein Bcl-2 and reduced expression of the pro-apoptotic protein Bax. These findings indicate that 6,6'-bieckol could be used as a potential nutraceutical agent offering protection against the glucotoxicity caused by hyperglycemia-induced oxidative stress associated with diabetes.

Growth Period Effects on the Protective Properties of Aloe vera Against t-BHP-Induced Oxidative Stress in Chang Cells.

Aloe vera has been used in traditional medicine for the therapy of a variety of disorders, such as wounds and burns. However, few studies have examined the antioxidant capacities of A. vera plants during different growth periods. In order to investigate the effects of growth on antioxidant activity, A. vera was prepared from 2-, 4-, 6-, 8-, and 12-month-old aloe. The extracts from 6-month-old A. vera showed the highest contents of flavonoids (9.750 mg catechin equivalent/g extract) and polyphenols (23.375 mg gallic acid equivalent/g extract) and the highest ferric reducing antioxidant power (0.047 mM ferrous sulfate equivalent/mg extract). The extract from 6-month-old A. vera exhibited the highest free radical scavenging potential, and the lowest IC50 values were found for 2,2-diphenyl-1-picrylhydrazyl (0.26 mg/ml) and alkyl radicals (0.50 mg/ml). In addition, the extract from 6-month-old A. vera showed the greatest effects on cell viability in normal liver cells. Based on these findings, the extract from 6-month-old A. vera was examined further in order to determine its protective potential against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress. The extract from 6-monthold A. vera at a concentration of 0.25 mg/ml showed the highest protective activity against t-BHP-induced reactive oxygen species production. These findings suggested that harvesting regimens were critical in the regulation of effects of the bioactive potential of A. vera on antioxidant activity.

Antioxidant activity and protective effect of extract of Celosia cristata L. flower on tert-butyl hydroperoxide-induced oxidative hepatotoxicity.

This study was undertaken to evaluate the antioxidant potential and protective effects of Celosia cristata L. (Family: Amaranthaceae) flower (CCF) extracts on tert-butyl-hydroperoxide (t-BHP)-induced oxidative damage in the hepatocytes of Chang cells and rat livers. In vitro, CCF extracts exhibited protective effect through their radical scavenging ability to enhance cell viability, prevent reactive oxygen species (ROS) generation, and inhibit mitochondrial membrane depolarisation in t-BHP-induced hepatotoxicity in Chang cells. In vivo, oral feeding of CCF (100mg and 500mg/kg of body weight) to rats for five consecutive days before a single dose of t-BHP (2mmol/kg, i.p.) showed a significant (p<0.05) protective effect by lowering serum levels of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). The extract decreased the hepatic levels of lipid peroxidation (MDA) and serum level of triglyceride (TG) against t-BHP-induced oxidative stress. These results indicate that CCF extract prevented oxidative stress-induced liver injury by enhancing hepatocyte antioxidant abilities.

Thymol from Thymus quinquecostatus Celak. protects against tert-butyl hydroperoxide-induced oxidative stress in Chang cells.

The present work describes the protective effects of thymol isolated from Thymus quinquecostatus Celak. against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage through various experiments with Chang liver cells. Thymol significantly protected hepatocytes against t-BHP-induced cell cytotoxicity as demonstrated by increased viability. Furthermore, observation of Hoechst staining, annexin V/PI staining, and expression of Bcl-2 and Bax indicated that thymol inhibited t-BHP-induced Chang cell damage. Further, thymol inhibited the loss of mitochondrial membrane potential in t-BHP-treated Chang cells and prevented oxidative stress-triggered reactive oxygen species (ROS) and lipid peroxidation (malondialdehyde, MDA). Thymol restored the antioxidant capability of hepatocytes including glutathione (GSH) levels which were reduced by t-BHP. These results indicated that thymol prevents oxidative stress-induced damage to liver cells through suppression of ROS and MDA levels and increase of GSH level.

Antioxidant activity and protective effects of Trapa japonica pericarp extracts against tert-butylhydroperoxide-induced oxidative damage in Chang cells.

In this study, the antioxidant properties of Trapa japonica pericarp extracts were evaluated through several biochemical assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH), alkyl radical scavenging activity, hydroxyl radical scavenging, ferric reducing antioxidant power (FRAP) assay, ABTS radical scavenging activity and oxygen radical absorbance capacity (ORAC). The antioxidant activities were compared with other natural and synthetic antioxidants. The results showed that higher radical scavenging activity and antioxidant capacity in FRAP than those of vitamin C as a positive control. T. japonica pericarp extracts have antioxidant properties through its ability to prevent tert-butylhydroperoxide (t-BHP)-induced toxicity which enhance the cell viability, reduce reactive oxygen species (ROS) production, inhibits of oxidative damage and mitochondria dysfunction in Chang liver cells. Therefore, based on these finding, it seems reasonable to suggest that T. japonica pericarp extracts has the potential to protect liver against t-BHP-induced cell damage and should be considered as a potential functional food.

Primo vascular system in the subarachnoid space of a mouse brain.

Objective. Recently, a novel circulatory system, the primo vascular system (PVS), was found in the brain ventricles and in the central canal of the spinal cord of a rat. The aim of the current work is to detect the PVS along the transverse sinuses between the cerebrum and the cerebellum of a mouse brain. Materials and Methods. The PVS in the subarachnoid space was analyzed after staining with 4',6-diamidino-2-phenylindole (DAPI) and phalloidin in order to identify the PVS. With confocal microscopy and polarization microscopy, the primo vessel underneath the sagittal sinus was examined. The primo nodes under the transversal sinuses were observed after peeling off the dura and pia maters of the brain. Results. The primo vessel underneath the superior sagittal sinus was observed and showed linear optical polarization, similarly to the rabbit and the rat cases. The primo nodes were observed under the left and the right transverse sinuses at distances of 3,763 µ m and 5,967 µ m. The average size was 155 µ m × 248 µ m. Conclusion. The observation of primo vessels was consistent with previous observations in rabbits and rats, and primo nodes under the transverse sinuses were observed for the first time in this work.

Antioxidant and DNA protection effects of taurine by electron spin resonance spectroscopy.

Taurine may play an important role in protecting cells against toxic injury by an antioxidant. However, there is a lack of evidence to support this hypothesis. The objective of this study was to examine the in vitro antioxidant properties of taurine against different reactive species at various concentrations. The radical scavenging effects of taurine on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical, superoxide radical, and alkyl radical were investigated using a spin-trapping electron method and compared with the electron spin resonance (ESR) signal intensity. ESR assays showed that DPPH radical scavenging activity of taurine at various concentrations (0.0625 ∼ 1 mg/mL) was elevated with a decrease of ESR signals in a dose-dependent manner. Moreover, taurine exhibited the radical scavenging activities against hydroxyl radicals, superoxide radicals, and alkyl radicals. Findings from this study suggest that taurine may be a useful radical scavenger and a potential supplement for the food, pharmaceutical, and cosmetic industries as well as feed and/or antibiotic because of its potent antioxidant capacities against various reactive radicals.

Primo vascular system in the subarachnoid space of the spinal cord of a pig.

The primo vascular system was recently observed in the central nervous systems of rabbits and rats, but no investigations in large animals have been reported. In the present work we found a putative primo vascular system in the spinal cord of a pig. We obtained spines from four healthy pigs and fixed them with paraformaldehyde. The primo vessels were expected to lie in the subarachnoid space between the pia mater and the arachnoid mater. The composite of three membranes (the pia, the arachnoid, and the dura maters) wrapping the spinal cord was peeled off, isolated from the spine, and put on a slide glass. This composite was stained with 4',6'-Diamidino-2-phenylindole (DAPI) and phalloidin to show the nuclei and the f-actin, respectively, in the cells of the primo vessels. We observed eleven pieces of the putative primo vessels in the subarachnoid space of the spines at the thoracic spinal nerve area. They had the typical rod-shaped nuclei distributed in a broken line, and f-actin signals around nuclei. The lengths of the nuclei were 12-15 µm, and the thicknesses of the primo vessels were 8∼20 µm, which were consistent with other primo vessels that had been observed in the various organs of rabbits, rats, and mice. In addition, we observed branching of the primo vessels, which is again an expected result from previous works. In conclusion, a primo vessel was observed in the subarachnoid space of the spinal cord of a pig. This was the first observation of a primo vessel in a large animal, and the staining method used to observe the primo vessel in a fixed sample was newly developed in this work.

In vitro protective effects of Thymus quinquecostatus Celak extracts on t-BHP-induced cell damage through antioxidant activity.

The purpose of this study was to evaluate the antioxidative activities of water and 70% ethanolic extracts from the Thymus quinquecostatus Celak (TQC) for natural antioxidant source. The antioxidant activities were compared with other natural and synthetic antioxidants. The levels of total polyphenols and flavonoids were also determined. The extracts were found to have different levels of antioxidant properties in a few kind of assay. The results showed that higher radical scavenging activity, reducing power and antioxidant capacity in FRAP than those of BHT as a positive control. In addition, the extracts from the TQC leaf and stem showed stronger antioxidant activity than that of vitamin C, α-tocopherol in ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. Cytoprotective and anti-apoptotic effect of water extracts from TQC was also prevented t-BHP-induced toxicity in Chang liver cells. Therefore, these results indicate that TQC extracts have antioxidant properties through its ability to enhance the cell viability, reduction of production of ROS, inhibition of oxidative damage, mitochondria dysfunction and ultimately inhibition of cell apoptosis. Based on the results described above, it is suggested that TQC has the potential to protect liver on t-BHP-induced cell damage and should be considered as a prospective functional food.

A double-blind randomized controlled comparison of APDDR-0901, a novel cosmeceutical formulation, and 0.1% adapalene gel in the treatment of mild-to-moderate acne vulgaris.

Topical retinoids have been widely used in the treatment of acne. They comprise several products used as prescription drugs as well as cosmeceuticals. Of these products, retinol has better tolerability compared with prescription retinoids such as tretinoin, but it is only used in cosmeceuticals due to its low biologic activity. A combination formulation could be an effective alternative to address the problem of decreased therapeutic activity. Recently, hexamidine diisethionate is known to have antibacterial activity, and rose extract has been shown to possess anti-inflammatory activity. In this study, we compared the efficacy and safety of the combination product APDDR-0901 (0.03% retinol, 0.7% rose extract, and 0.05% hexamidine diisethionate) vs 0.1% adapalene gel for the treatment of mild-to-moderate acne. This 12-week, multicenter, double-blinded study included 97 patients with mild-to-moderate acne. Efficacy was evaluated using 4 discrete variables: lesion count, acne grade, physician-assessed global improvement, and patient self-assessment. We also assessed safety profiles, including cutaneous irritation. Both APDDR-0901 and adapalene showed significant improvements without significant differences. Otherwise, the APDDR-0901 group showed better safety profiles, particularly in the first 2 weeks. In conclusion, APDDR-0901 could be an effective and safe alternative in the treatment of mild-to-moderate acne.