Metabolic profile of Phellodendron amurense Rupr. in vivo of rat and its metabolomic study on intervention in rheumatoid arthritis.

To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100 mm × 2.1 mm, 1.7 µm), the mobile phase was acetonitrile-0.1% formic acid aqueous solution (gradient elution). Prior to and following the administration of the decoction of PAC, the samples of blood, urine, and fecal were collected from the rats, in the positive ion mode, pharmacogenic metabolites in each biological sample were identified according to the accurate mass, fragment ions, retention time, metabolic reaction type, comparison of reference substance and retrieval of Pub Med database; The adjuvant-type arthritis (AA) rat model was established, and blood metabonomics method was used to study the improvement effect of rheumatoid arthritis after drug intervention with PAC, and its mechanism was preliminarily explored through analysis of metabolic pathway. A total of 72 exogenous components were identified, including 17 prototype components and 55 metabolites; 14 biomarkers were screened by blood metabolomics techniques combined with multivariate statistical analysis, and PAC significantly improved symptoms of rheumatoid arthritis in rats, and the metabolic pathway analysis mainly involves 5 metabolic pathways. The components in the aqueous decoction of PAC mainly undergo phase I metabolic reactions in rats, such as oxidation, reduction, dehydrogenation, demethylation, and phase II metabolic reactions, such as acetylation, glucuronidation, methylation; PAC has anti-rheumatoid arthritis effects, and its mechanism of action may be related to biosynthesis of aminoacyl-tRNA, metabolism of phenylalanine, metabolism of tryptophan, degradation of valine, leucine and isoleucine and biosynthesis of pantothenic acid and coenzyme A, providing a scientific basis for the study of the pharmacodynamic substances and the action mechanism of PAC against RA.

Protective Effects of Phellodendron Species on Bone Health: A Novel Perspective on Their Potentials in Treating Osteoporosis and Osteoarthritis.

Phellodendron (PN) species, traditionally used in Chinese medicine for centuries, hold promise as a potential treatment for osteoporosis (OP) and osteoarthritis (OA) due to their bioactive compounds. The bioactive compounds, including berberine and palmatine, exhibit anti-inflammatory, antioxidant, and bone-protective properties, contributing to their potential therapeutic benefits in promoting bone health and preventing bone loss. However, challenges such as the need for standardized preparation and dosing, limited clinical studies, and potential interactions with other medications hinder their clinical use. Nonetheless, the rich history of PN species in Chinese medicine provides a promising foundation for future investigation into their potential as alternative treatments for OP and OA. Further research is needed to fully understand the underlying mechanisms of action and explore the clinical implications of PN for bone health.

Integrated Transcriptomic and Metabolomic Analysis Reveals the Mechanism of Gibberellic acid Regulates the Growth and Flavonoid Synthesis in Phellodendron chinense Schneid Seedlings.

The phytohormone gibberellic acids (GAs) play a crucial role in the processes of growth, organ development, and secondary metabolism. However, the mechanism of exogenous GA3 regulating the growth and flavonoid synthesis in Phellodendron chinense Schneid (P. chinense Schneid) seedlings remains unclear. In this study, the physicochemical properties, gene expression level, and secondary metabolite of P. chinense Schneid seedlings under GA3 treatment were investigated. The results showed that GA3 significantly improved the plant height, ground diameter, fresh weight, chlorophyll content, soluble substance content, superoxide dismutase, and peroxidase activities. This was accompanied by elevated relative expression levels of Pc(S)-GA2ox, Pc(S)-DELLA, Pc(S)-SAUR50, Pc(S)-PsaD, Pc(S)-Psb 27, Pc(S)-PGK, Pc(S)-CER3, and Pc(S)-FBA unigenes. Conversely, a notable reduction was observed in the carotenoid content, catalase activity and the relative expression abundances of Pc(S)-KAO, Pc(S)-GID1/2, and Pc(S)-GH 3.6 unigenes in leaves of P. chinense Schneid seedlings (p < 0.05). Furthermore, GA3 evidently decreased the contents of pinocembrin, pinobanksin, isosakuranetin, naringin, naringenin, (-)-epicatechin, tricetin, luteolin, and vitexin belonged to flavonoid in stem bark of P. chinense Schneid seedlings (p < 0.05). These results indicated that exogenous GA3 promoted growth through improving chlorophyll content and gene expression in photosynthesis and phytohormone signal pathway and inhibited flavonoid synthesis in P. chinense Schneid seedlings.

Separation and purification of alkaloids and phenolic acids from Phellodendron chinense by pH-zone refining and online-storage inner-recycling counter-current chromatography.

In this work, eight compounds from Phellodendron chinense were separated and purified by pH-zone refining counter-current chromatography and traditional counter-current chromatography coupled with online-storage inner-recycling counter-current chromatography (IRCCC). The pH-zone-refining mode was adopted for separating 2.0 g of crude extract with the solvent system of chloroform-methanol-water (4:3:3, v/v), in which 10 mM hydrochloric acid and 10 mM triethylamine were added in the stationary and mobile phases, respectively. Meanwhile, traditional counter-current chromatography coupled with online-storage IRCCC separation was performed by the solvent system of n-hexane-ethyl acetate-methanol-water (5:5:2:8, v/v). Finally, eight compounds, including six alkaloids as 6-methylpiperidin-2-one(1), isoplatydesmine(4), berlambine(5), epiberberine(6), palmatine(7), berberine(8) and two phenolic acids as ferulic acid(2), isoferulic acid(3), were successfully obtained using these three different CCC modes with the purities over 95.0%.

Study on chemical constituents and fingerprints of Phellodendron amurense Rupr. based on ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry.

The chemical constituents from Phellodendron amurense Rupr. were characterized systematically by ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry method for collecting mass spectrometry data, and the fingerprints method was established, providing reference for its quality control. The chromatographic column was ACQUITY UPLC BEH-C18 (100 mm×2.1 mm, 1.7 µm). The mobile phase was acetonitrile-0.1% formic acid aqueous solution and the compounds from P. amurense Rupr. were identified by Qualitative Analysis 10.0 software, reference substance, retention time, mass spectrometry fragmentation pattern and database retrieval. Meanwhile, liquid chromatography-mass spectrometry fingerprint methods of P. amurense Rupr. and Phellodendron chinense Schneid. were established by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine (2012 edition), and the differences were analyzed by multivariate statistical analysis methods. A total of 105 compounds were identified, including 102 alkaloids, two phenolic acids, and one lactone compound. Liquid chromatography-mass spectrometry fingerprint method was established with ideal precision, stability and repeatability, and 12 quality differential markers were recognized between the above two herbs. Liquid chromatography-mass spectrometry method can be used for qualitative analysis of the constituents of Phellodendron amurense Rupr., providing reference for clarifying the material basis and promoting the clinical precision medication and quality evaluation of P. amurense Rupr.

[Characterization and identification of alkaloids in Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex based on UHPLC-IM-Q-TOF-MS].

A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.

Identifying Genes Associated with Female Flower Development of Phellodendron amurense Rupr. Using a Transcriptomics Approach.

Phellodendron amurense Rupr., a species of Rutaceae, is a nationally protected and valuable medicinal plant. It is generally considered to be dioecious. With the discovery of monoecious P. amurense, the phenomenon that its sex development is regulated by epigenetics has been revealed, but the way epigenetics affects the sex differentiation of P. amurense is still unclear. In this study, we investigated the effect of DNA methylation on the sexual development of P. amurense. The young inflorescences of male plants were treated with the demethylation agent 5-azaC, and the induced female flowers were obtained. The induced female flowers' morphological functions and transcriptome levels were close to those of normally developed plants. Genes associated with the development of female flowers were studied by comparing the differences in transcriptome levels between the male and female flowers. Referring to sex-related genes reported in other plants, 188 candidate genes related to the development of female flowers were obtained, including sex-regulating genes, genes related to the formation and development of sexual organs, genes related to biochemical pathways, and hormone-related genes. RPP0W, PAL3, MCM2, MCM6, SUP, PIN1, AINTEGUMENTA, AINTEGUMENTA-LIKE6, AGL11, SEUSS, SHI-RELATED SEQUENCE 5, and ESR2 were preliminarily considered the key genes for female flower development. This study has demonstrated that epigenetics was involved in the sex regulation of P. amurense, with DNA methylation as one of its regulatory modes. Moreover, some candidate genes related to the sexual differentiation of P. amurense were obtained with analysis. These results are of great significance for further exploring the mechanism of sex differentiation of P. amurense and studying of sex differentiation of plants.

Characterization of a putative novel higrevirus infecting Phellodendron amurense Rupr. in China.

Phellodendron-associated higre-like virus (PaHLV) was identified in Phellodendron amurense Rupr. in China. Three near-full-length sequences of the viral genomic RNAs (RNA1-RNA3) were first obtained by RNA-seq, and their complete sequences were then determined by RT-PCR, 5'-RACE, and 3'-RACE. RNA1-3 of PaHLV were determined to be 8,183, 3,062, and 3,998 nucleotides (nt) in length, respectively, excluding the poly(A) tail. All of the viral proteins encoded by PaHLV shared the highest amino acid sequence identity (44.8-78.1%) with the unclassified kitavirid pistachio virus X (PiVX, MT334618-MT334620) from Iranian pistachio. Sequence comparisons and phylogenetic analysis also showed PiVX to be the closest relative of PaHLV and supported their inclusion in the genus Higrevirus, family Kitaviridae. Thus, PaHLV is proposed to be a member of a new species in this genus, for which we suggest the binomial name "Higrevirus amur".

An in vitro study of the effects of Phellodendron bark extract and berberine chloride on periodontal pathogenic bacteria in the oral microbiome.

OBJECTIVES: Periodontal disease is triggered by oral microbiome dysbiosis. Thus, to prevent its onset, it is important to maintain relative abundance of periodontal pathogenic bacteria in the oral microbiome at a low level. While Phellodendron bark extract (PBE) and its active ingredient, berberine, exert antibacterial effects on periodontal pathogenic bacteria, such as Porphyromonas gingivalis, their effects on the oral microbiome as a whole remain unknown. Therefore, we aimed to clarify the potential of PBE and berberine chloride (BC) in regulating the relative abundance of periodontal pathogenic bacteria in the oral microbiome. METHODS: Saliva was collected from 20 participants. Each participant's saliva was combined separately with P. gingivalis suspension and either PBE or BC in a modified basal medium. The samples were then incubated under anaerobic conditions for 24 h. After cultivation, we determined the total bacterial concentration using quantitative polymerase chain reaction analysis and the bacterial composition using 16 S ribosomal RNA gene sequencing. RESULTS: The total bacterial concentration was reduced because of treatment with PBE and BC. Bacterial 16 S ribosomal RNA gene sequencing confirmed that treatment with PBE and BC significantly reduced the relative abundance of periodontal pathogenic bacteria, including red and orange complex bacteria. CONCLUSIONS: Our findings suggest that PBE and BC reduce the relative abundance of periodontal pathogenic bacteria in the oral microbiome. Thus, PBE and BC can aid in preventing periodontal disease, given their ability to regulate the oral microbiome composition and their anti-inflammatory effects.

Dissection of transcriptome and metabolome insights into the isoquinoline alkaloid biosynthesis during stem development in Phellodendron amurense (Rupr.).

Phellodendron amurense (Rupr.) is a well-known medicinal plant with high medicinal value, and its various tissues are enriched in various active pharmaceutical ingredients. Isoquinoline alkaloids are the primary medicinal component of P. amurense and have multiple effects, such as anti-inflammation, antihypertension, and antitumor effects. However, the potential regulatory mechanism of isoquinoline alkaloid biosynthesis during stem development in P. amurense is still poorly understood. In the present study, a total of eight plant hormones for each stem development stage were detected; of those, auxin, gibberellins and brassinosteroids were significantly highly increased in perennial stems and played key roles during stem development in P. amurense. We also investigated the content and change pattern of secondary metabolites and comprehensively identified some key structural genes involved in the isoquinoline alkaloid biosynthesis pathway by combining the transcriptome and metabolomics. A total of 39,978 DEGs were identified in the present study, and six of those had candidate structural genes (NCS, GOT2, TYNA, CODM, TYR, TAT and PSOMT1) that were specifically related to isoquinoline alkaloid biosynthesis in P. amurense. Corydalmine, cyclanoline, dehydroyanhunine, (S)-canadine and corybulbine were the most significantly upregulated metabolites among the different comparative groups. Three differentially expressed metabolites, dopamine, (S)-corytuberine and (S)-canadine, were enriched in the isoquinoline alkaloid biosynthesis pathway. Furthermore, bHLH and WRKY transcription factors play key roles in the isoquinoline alkaloid biosynthesis pathway in P. amurense. The results not only provide comprehensive genetic information for understanding the molecular mechanisms of isoquinoline alkaloid biosynthesis but also lay a foundation for the combinatory usage of the medicinal active ingredient of P. amurense.

Efficacy and Clinical Value of Negative-Pressure Wound Therapy with Instillation (NPWTi) of Compound Phellodendron Liquid in the Treatment of Diabetic Foot Ulcer: A Prospective Cohort Study.

Objective: To evaluate the efficacy and application value of compound Phellodendron liquid (CPL) for negative-pressure wound therapy with instillation (NPWTi) in the treatment of diabetic foot ulcers by observing the improvement of diabetic foot ulcers. Methods: Sixty patients with diabetic foot ulcers who met the inclusion criteria were admitted to the Department of Peripheral Blood Vessels (Wound Repair) of Chongqing Hospital of Traditional Chinese Medicine from August 2020 to August 2021. The random number table method divided it into the CPL NPWTi group and normal saline NPWTi group, with 30 cases in each group. The experimental group adopted FufangHuangbaiye for NPWTi, and the control group used normal saline for NPWTi. The treatment effect was evaluated by baseline index, wound healing observation index, inflammatory factor index, pain scores during dressing change, and the number of days in hospital. Results: After 10 days of treatment, the symptom integration, procalcitonin (PCT), and C reactive protein (CRP) of the CPL NPWTi group were significantly reduced compared with the normal saline NPWTi group, while there was no obvious difference between wound area and erythrocyte sedimentation rate (ESR). The wound area, symptom integral, PCT, ESR, and CRP of the CPL NPWTi group were significantly reduced compared with the normal saline NPWTi group after treatment for 20 days and 30 days. The positive proportion of bacterial culture in the CPL NPWTi group was significantly reduced compared with the normal saline NPWTi group after treatment for 10 days, 20 days, and 30 days. After treatment, the pain scores during dressing change and the number of days in hospital in normal saline NPWTi group were significantly lower than those in the CPL NPWTi group. Conclusion: Compound Phellodendron liquid NPWTi therapy can improve diabetic foot ulcers, providing a safe and effective method for treating diabetic foot ulcers.

Direct infusion electrospray ionization-ion mobility-mass spectrometry for rapid metabolite marker discovery of medicinal Phellodendron Bark.

Ion-mobility mass spectrometry (IM-MS) currently serves as a powerful tool for the structural identification of numerous biological compounds and small molecules. In this work, rapid metabolomic analysis of closely-related herbal medicines by direct injection ion mobility-quadrupole time-of-flight mass spectrometry (DI-IM-QTOF MS) was established. Phellodendron chinense Bark (PC) and Phellodendron amurense Bark (PA) were studied as a case. Thirty-three batches of PC and twenty-two batches of PA have been directly injected in electrospray ionization-IM-QTOF MS in positive mode. Without chromatographic separation, each run was completed within 3 min. After data alignment and statistical analysis, a total of seven chemical markers were found (p-value < 0.05, VIP > 1.00). Among them, the ion m/z 342.17 and m/z 356.18 present a single peak in the drift spectrum, respectively, but their drift time has a certain deviation compared with the pure substance of known compounds. In addition, the MS/MS spectra also confirmed that the single peak includes two chemical isomers. To investigate the composition ratio of individual isomers, the calibration curves of relative drift time (rDT) based on the standard superposition method were established, which were found to fit the least square regression. The ion [M]+m/z 342.17 was recognized consisting of magnoflorine (MAG) and phellodendrine (PHE), and their composition ratio in PA and PC samples was calculated. The results were compared with those obtained by the HPLC quantitative method, which produced equivalent quantification results. Our DI-IM-QTOF MS methodology provides an additional methodology for the relative quantification of unresolved isomers in drift tube IM-MS and offers DI-IM-QTOF MS based metabolomics.

Deciphering the Q-markers of nourishing kidney-yin of Cortex Phellodendri amurense from ZhibaiDihuang pill based on Chinmedomics strategy.

BACKGROUND: Cortex Phellodendri amurensis (CPA) has high medicinal value in the treatment of kidney-yin deficiency diseases. However, due to the lack of research on the therapeutic material basis of CPA, the current quality control standard for CPA is defective, and the effect of the nourishing kidney-yin of CPA was limited. PURPOSE: Based on the principle of correspondence between the syndrome and prescriptions, we studied the CPA in ZhibaiDihuang pill (ZBDH) to identify quality markers (Q-markers) of CPA in ZBDH for treating kidney-yin deficiency and seek the potential Q-markers of CPA under nourishing kidney-yin effect combined with the analysis of single CPA. METHODS: Taking Chinmedomics as the core strategy, metabonomics analysis and effective component identification were performed by UPLC-MS. RESULTS: A total of 121 chemical components of ZBDH were identified, among which the contents of berberine, palmatine, jatrorrhizine and magnoflorine changed the most obviously with the addition of CPA. Forty-five components were identified in the blood in the markedly effective state, including berberine, palmatine, jatrorrhizine and magnoflorine. The therapeutic material basis of ZBDH in the treatment of kidney-yin deficiency was found, and 6 components were found to derive from CPA, including magnoflorine and jatrorrhizine. In addition, seventeen components were identified in the blood in the single CPA treatment, including berberine, palmatine, jatrorrhizine and magnoflorine. CONCLUSIONS: Magnoflorine and jatrorrhizine were the Q-markers of CPA for treating kidney-yin deficiency in the formula of ZBDH and they were also potential Q-markers of the nourishing kidney-yin of CPA.

Structural elucidation and anti-diabetic osteoporotic activity of an arabinogalactan from Phellodendron chinense Schneid.

Phellodendron chinense Schneid. was widely used as a medicinal herb for the treatment of diabetic osteoporosis in China. In this study, an arabinogalactan, named as PPCP-1, was isolated from the bark of Phellodendron chinense Schneid., and purified by DEAE-cellulose DE52 and Sephacryl S-200 HR column chromatography. The structure of PPCP-1 was characterized as a repeating unit consisting of →3)-ß-d-Galp-(1→, →3,6)-ß-d-Galp-(1→, →5)-α-l-Araf-(1→, →4)-α-d-Glcp-(1→, →3)-α-d-Glcp-(1→, →4)-α-d-Manp-(1→ with branches of →5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→ and terminal α-l-Araf. Pharmacologically, the oral administration of PPCP-1 preserved osteoporosis associated with hyperglycemia by inhibiting α-glucosidase activity, improving glucose tolerance, decreasing the accumulation of advanced glycation end products (AGEs), as well as down-regulating the expression of receptor for AGEs in tibias of streptozotocin-induced diabetic rats. Collectively, the present study suggested that the arabinogalactan PPCP-1 from Phellodendron chinense Schneid. might potentially be used as functional foods for bone health and/or developed for drug discovery for alleviating diabetic osteoporosis.

Isolation and characterization of phellodendronoside A, a new isoquinoline alkaloid glycoside with anti-inflammatory activity from Phellodendron chinense Schneid.

Bark of Phellodendron chinense Schneid. (Rutaceae), called "Huang Bai" in China, is one of the 50 most used Chinese medicines in clinical practice. In this paper, a new isoquinoline alkaloid glycoside was isolated from P. chinense, and its structure was elucidated using spectroscopic method. The compound was eventually identified as (1S, 3"S)-1, 2, 3, 4-tetrahydro-7-hydroxy-1-[(4-hydroxybenzyl) methyl]-2-methyl-8-O-isoquinolinyl-[3-hydroxy-3-methylglutaryl]-ß-D-glucopyranoside and named as Phellodendronoside A (PDA). The results of molecular docking showed that PDA could stably bind to an extracellular signal-regulated kinase (ERK), stress-activated protein kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) proteins that are closely related to inflammation. Further, the anti-inflammatory activity of PDA was evaluated using the lipopolysaccharide (LPS) induced RAW264.7 macrophage model. We observed that PDA can effectively reduce the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and decrease the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, we found that PDA inhibits the activation of ERK, JNK and p38MAPK proteins in the MAPK signaling pathway. Collectively, the present study demonstrates that PDA has excellent anti-inflammatory effect in vitro by inhibiting the overproduction of pro-inflammatory mediators, and its mechanism of action involves suppressing the activation of MAPK pathways, suggesting that PDA may be a potential agent for the treatment of inflammatory illness.

Exploration of yellow-emitting phosphors for white LEDs from natural resources.

White light-emitting diodes (LEDs) are widely used in various lighting fields as a part of energy-efficient technology. However, some shortcomings of luminescent materials for white LEDs, such as complexity of synthesis, high cost, and harmful impact on the environment, limit their practical applications to a large extent. In this respect, the present work aims to study the ability of using Berberine (BBR) chloride extracted from Rhizoma coptidis and Phellodendron Chinese herbs as yellow phosphor for white LEDs. For this, white LEDs were successfully fabricated by applying 0.006 g of BBR chloride onto the blue LED chips (450 nm). The produced LEDs exhibited good luminescence properties at a voltage of 2.4 V along with eco-friendly characteristics and low cost. The Commission International de l'Eclairage chromaticity, the correlated color temperature, and the color rendering index were determined to be (${x} = {0.32}$, ${y} = {0.33}$), 5934 K, and 74, respectively. Therefore, BBR chloride is a suitable environmentally friendly and easily accessible yellow phosphor for white LEDs.

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named "Tong Feng", which is described as "ache in bones and joints" with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. AIM OF THE STUDY: Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). MATERIALS AND METHODS: Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine, phellodendrine, magnoflorine, jatrorrhizine, berberrubine, palmatine, and tetrahydropalmatine, in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. RESULTS: PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. CONCLUSIONS: The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.

Phellodendron amurense Extract Protects Human Keratinocytes from PM2.5-Induced Inflammation via PAR-2 Signaling.

Dietary supplement and personal care products aiming to provide protection from air pollution have been of great interest for decades. Epidemiology demonstrated that PM10 and PM2.5 particulate matter (PM) are an actual threat to public health worldwide, but the detailed processes of how these particles attack the cells are not fully understood. Here, we report that the measurement of intracellular calcium concentration ([Ca2+]i) using human respiratory or skin cells can illustrate pollutant challenges by triggering Ca2+ influx in these cells. This signal was generated by proteinase-activated receptor-2 (PAR-2), confirmed by competition analyses, and Phellodendron amurense bark extract (PAE), a traditional medicine, was able to control the response and expression of PAR-2. Increase in proinflammatory cytokines and decrease in cell adhesion components could suggest a severe damage status by air pollutants and protection by PAE. Finally, we identified 4-O-feruloylquinic acid (FQA), an active compound of PAE, showing the same effects on Ca2+ influx and PAR-2 regulation. The results presented here should help understand the underlying mechanism of PM insults and the beneficial effect of standardized PAE as dietary supplement or cosmetical ingredient.

Effects of a complex mixture prepared from agrimonia, houttuynia, licorice, peony, and phellodendron on human skin cells.

Active ingredients derived from natural sources are widely utilized in many industries. Cosmetic active ingredients are largely derived from various plants. In this study, we examined whether a mixture of plant extracts obtained from agrimonia, houttuynia, licorice, peony, and phellodendron (hereafter AHLPP), which are well-known for their effects on skin, could affect skin barrier function, inflammation, and aging in human skin cells. We also determined whether AHLPP extracts sterilized using γ-irradiation (to avoid preservatives) retained their skin cell regulating activity. The AHLPP mixture could downregulate representative pro-inflammatory cytokines including IL 1-ß and IL 7. Procollagen peptide synthesis was also increased by AHLPP treatment along with mRNA upregulation of barrier proteins such as filaggrin and desmoplakin. The AHLPP mixture showed an anti-aging effect by significantly upregulating telomerase activity in human keratinocytes. We further observed TERT upregulation and CDKN1B downregulation, implying a weakening of pro-aging signal transduction. Co-cultivation of a hydrogel polymer containing the AHLPP mixture with human skin cells showed an alteration in skin-significant genes such as FLG, which encodes filaggrin. Thus, the AHLPP mixture with or without γ-irradiation can be utilized for skin protection as it alters the expression of some significant genes in human skin cells.

Multicenter Clinical Trials Analyzing Efficacy and Safety of Topical Cortex Phellodendri Compound Fluid in Treatment of Diabetic Foot Ulcers.

BACKGROUND The aim of this study was to analyze the clinical application of cortex phellodendri compound fluid (CPCF) in the treatment of diabetic foot ulcers. MATERIAL AND METHODS From January 2012 to December 2015, a total of 720 cases of diabetic foot ulcers (DFU) were randomly assigned into an experimental group (n=540) that was treated by CPCF and a control group (n=180) that was treated by a Kangfuxin solution (KFS). After 4 weeks of treatment, their ulcer area, serum growth factor, clinical total effective rate, and incidence of adverse events were assessed. RESULTS There were 720 patients who completed the trial. The experimental group was superior to the control group in reducing ulcer area, increasing growth factor content, and total effective rate (P<0.05). There was no significant difference in the adverse events rates between the 2 groups. CONCLUSIONS CPCF external treatment of diabetic foot ulcer can promote ulcer healing and increase the concentration of growth factors, and it is safe and reliable.