Phytochemistry, synthesis, analytical methods, pharmacological activity, and pharmacokinetics of loganin: A comprehensive review.

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.

Updated Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of Natural Product Geniposide.

At present, the potential of natural products in new drug development has attracted more and more scientists' attention, and natural products have become an important source for the treatment of various diseases or important lead compounds. Geniposide, as a novel iridoid glycoside compound, is an active natural product isolated from the herb Gardenia jasminoides Ellis (GJ) for the first time; it is also the main active component of GJ. Recent studies have found that geniposide has multiple pharmacological effects and biological activities, including hepatoprotective activity, an anti-osteoporosis effect, an antitumor effect, an anti-diabetic effect, ananti-myocardial dysfunction effect, a neuroprotective effect, and other protective effects. In this study, the latest research progress of the natural product geniposide is systematically described, and the pharmacological effects, pharmacokinetics, and toxicity of geniposide are also summarized and discussed comprehensively. We also emphasize the major pathways modulated by geniposide, offering new insights into the pharmacological effects of geniposide as a promising drug candidate for multiple disorders.

Evidences of Biomimetic and Nonantibiotic Characteristics of the Zinc-Carboxymethyl Chitosan-Genipin Organometallic Complex and Its Biocompatibility Aspects.

Bioinspired nonantibiotics can prove to be a better and an efficient tool to fight against antimicrobial resistance. In our study, biomaterial composed of zinc-carboxymethyl chitosan (CMC)-genipin was investigated for this purpose. Briefly, CMC was synthesized and transformed to porous scaffolds using the freeze drying method. The scaffolds were cross-linked and stabilized with genipin and zinc (2 M zinc acetate), respectively. FTIR spectroscopic data testified Zn complex formation and pointed out the absence of water molecule like that of zinc motif containing proteins. Hence, the complex may be termed as biomimetic. Genipin (0.5%) cross-linking appeared to contribute additively to the wet compressive strength of the zinc-CMC scaffolds. Biodegradation data revealed better stability of CMC-genipin-zinc scaffolds in enzymatic and nonenzymatic conditions than their redundant controls. The scaffolds seem to support adhesion and proliferation of human dental pulp stem cells and were hemocompatible to human red blood corpuscles, as revealed by scanning electron microscopy. The scaffolds were found to be antibacterial and mildly antibiofilm when tested against biofilm-forming bacteria, that is, Staphylococcus aureus (ATCC 9144), making it a potential nonantibiotic-like biomaterial. To conclude, this organometallic complex-based biomaterial may potentially serve as a weapon against antimicrobial resistance. Furthermore, the biomaterial potentially finds its application in dental, maxillofacial, and orthopedic tissue engineering applications.

Health-promoting properties of oleocanthal and oleacein: Two secoiridoids from extra-virgin olive oil.

Extra virgin olive oil (EVOO) polyphenols, including the secoiridoids oleocanthal (OLC) and oleacein (OLE), are attracting attention because of their beneficial effects on health. Data on OLC and OLE bioavailability are scarce, as most research on EVOO polyphenols has concentrated on hydroxytyrosol, tyrosol, and oleuropein. Consequently, relevant goals for future research are the elucidation of OLC and OLE bioavailability and finding evidence for their beneficial effects through pre-clinical and clinical studies. The aim of this review is to shed light on OLC and OLE, focusing on their precursors in the olive fruit and the impact of agronomic and processing factors on their presence in EVOO. Also discussed are their bioavailability and absorption, and finally, their bioactivity and health-promoting properties.

Identification of prototypes from Ligustri Lucidi Fructus in rat plasma based on a data-dependent acquisition and multicomponent pharmacokinetic study.

The identification and quantization of traditional Chinese medicine (TCM) are a challenge for researchers and industry. Using untargeted analytical methods, the in vivo detection and identification of TCM compounds are difficult because of the significant interference of endogenous substances. Fortunately, the ongoing development of new analytical technologies, especially Q-Orbitrap-MS, offers some solutions. Our team developed a holistic MS method, combining untargeted data-dependent MS2 (dd-MS2 ) modes to extensively identify TCM prototypes in vivo. The method was successfully applied to the analysis of Ligustri Lucidi Fructus (LLF). LLF is a widely used TCM with a remarkable nourishing effect on the liver and kidney. In the study, we aimed to identify the prototypes in rat plasma after oral administration of LLF extract. Following separation on an HSS T3 column, LLF extract and rat plasma were performed in untargeted dd-MS2 mode. Forty-seven compounds were characterized in rats plasma as prototypes of LLF extract. Furthermore, seven major prototypes were chosen as pharmacokinetic markers to investigate LLF's pharmacokinetic properties. The results provides comprehensive determination of compounds in LLF both in vitro and in vivo, which is important for quality control, pharmacology studies and clinical use of LLF.

Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics.

Iridoids are a class of active compounds that widely exist in the plant kingdom. In recent years, with advances in phytochemical research, many compounds with novel structure and outstanding activity have been identified. Iridoid compounds have been confirmed to mainly exist as the prototype and aglycone and Ι and II metabolites, by biological transformation. These metabolites have been shown to have neuroprotective, hepatoprotective, anti-inflammatory, antitumor, hypoglycemic, and hypolipidemic activities. This review summarizes the new structures and activities of iridoids identified locally and globally, and explains their pharmacokinetics from the aspects of absorption, distribution, metabolism, and excretion according to the differences in their structures, thus providing a theoretical basis for further rational development and utilization of iridoids and their metabolites.

Deciphering the absorption profile and interaction of multi-components of Zhi-Zi-Da-Huang decoction based on in vitro-in silico-in vivo integrated strategy.

Zhi-Zi-Da-Huang decoction (ZZDHD) has been acknowledged with striking therapeutic effects for hepatobiliary disorders in the history of China. As decoctions are usually administrated orally, intestinal absorption, the prerequisite task of exerting therapeutic effects, is of utmost significance for screening potential active compounds and understanding the mechanism of drug action. In this work, an in vitro-in silico-in vivo strategy based on HPLC-DAD-ESI-TOF/MS was adopted for precisely profiling the intestinal absorption of ZZDHD, which integrated information obtained from rat everted gut sac model, octanol-water partition model, in silico prediction and in vivo experimental data. Besides, 34 main absorbed ingredients were selected as chemical markers to investigate the compatible interaction of the decoction on absorption level using rat everted gut sac experiment. In total, 106 compounds of ZZDHD were speculated as potential absorptive. Among them, 90 constituents predicted absorbable in at least two experimental models were finally recognized as intestinal absorbable ingredients. In addition, the absorption level of iridoids, terpenoids and flavonoid glycosides were found improved and the absorption of catechins and anthraquinones were inhibited after prescription compatibility. Taken together, this study presents a reliable strategy for evaluating intestinal absorption of herbal medicines and offers a reference for the rationality of herbal compatibility and the modernization of traditional Chinese medicine (TCM).

UHPLC-MS/MS analysis of sphingosine 1-phosphate in joint cavity dialysate and hemodialysis solution of adjuvant arthritis rats: Application to geniposide pharmacodynamic study.

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P. Therefore, S1P can also be potentially used as a pharmacodynamic marker to study adjuvant arthritis (AA) rats. In the current study, a UHPLC-MS/MS method combined with the microdialysis sampling technique (using FTY720 phosphate as an internal standard) was adopted and validated to measure S1P levels in the hemodialysis fluid and joint cavity dialysates of AA rats after oral administration of GE. A S1P concentration-time curve in the dialysate was established in this study. It was demonstrated that GE exerted an anti-inflammatory effect by reducing AA-induced elevated S1P levels. It is showed that changes in S1P concentrations over time can be used to monitor the pharmacodynamic effects of GE in treating AA rats in pharmacodynamic studies.

Comparative pharmacokinetic study of four major bioactive components after oral administration of Zhi-Zi-Hou-Po decoction in normal and corticosterone-induced depressive rats.

A highly selective and efficient LC-MS/MS method was developed to determine the plasma concentration of magnolol, hesperidin, neohesperidin and geniposide following oral administration of Zhi-Zi-Hou-Po decoction in normal and depressed rats. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an XTerra® MS C18 column using a gradient elution with a mobile phase composed of acetonitrile-0.1% aqueous formic acid. The proposed method was validated to be specific, accurate and precise for the analytes determination in plasma samples. The calibration curves displayed good linearity over definite concentration ranges for the analytes. The intra- and inter-day precision of the proposed method at three different levels were all within <11.13% and the relative errors ranged from -8.46 to 8.93%. The recovery of the four compounds ranged from 82.72 to 89.08% and no apparent matrix effect was observed during sample analysis. After full validation, the established method was successfully applied for comparing the pharmacokinetics of four components between normal and depressed rats. The results showed that the AUC and Cmax of four analytes in depressed rats were significantly different from those in normal rats and might provide helpful information to guide the clinical use of Zhi-Zi-Hou-Po to treat depression.

Evaluation of the Hepatotoxicity of the Zhi-Zi-Hou-Po Decoction by Combining UPLC-Q-Exactive-MS-Based Metabolomics and HPLC-MS/MS-Based Geniposide Tissue Distribution.

With traditional Chinese medicine (TCM) becoming widespread globally, its safety has increasingly become a concern, especially its hepatoxicity. For example, Gardenia jasminoides Ellis is a key ingredient in the Zhi-Zi-Hou-Po decoction (ZZHPD), which is a commonly-used clinically combined prescription of TCM that may induce hepatoxicity. However, the underlying toxicity mechanism of ZZHPD is not fully understood. In this study, a plasma metabolomics strategy was used to investigate the mechanism of ZZHPD-induced hepatotoxicity through profiling entire endogenous metabolites. Twenty-four Sprague-Dawley rats were randomly assigned into four groups, which were orally administered with 0.9% saline, as well as 2.7 g/kg/day, 8.1 g/kg/day, or 27 g/kg/day of ZZHPD for 30 consecutive days, respectively. Biochemical assay and metabolomics assay were used to detect serum and plasma samples, whilst histopathological assay was used for detecting liver tissues, and the geniposide distribution in tissues was simultaneously measured. The results showed that the concentration of 20 metabolites linked to amino acid, lipid, and bile acid metabolism had significant changes in the ZZHPD-treated rats. Moreover, toxic effects were aggravated with serum biochemical and histopathological examines in liver tissues as the dosage increased, which may be associated with the accumulation of geniposide in the liver as the dosage increased. Notably, our findings also demonstrated that the combined metabolomics strategy with tissue distribution had significant potential for elucidating the mechanistic complexity of the toxicity of TCM.

[Pharmacokinetics of Achyranthes bidentata on adjuvant arthritis rats by microdialysis and UHPLC-MS/MS].

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 µg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg~(-1)+60 mg·kg~(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.

Metabolite profile analysis and pharmacokinetic study of emodin, baicalin and geniposide in rats.

1. Emodin, baicalin and geniposide are the major bioactive components in Da-Huang, Huang-Qin and Zhi-Zi which are herbal medicines widely used in Asian nations. 2. The metabolism of the three compounds was found to undergo hydroxylation, decarboxylation, dehydration, methylation, hydrolysis, hydrogenation, dihydrogenation, sulfation, glucosidation and/or glucuronidation. A total of 63 metabolites were detected in urine, plasma and bile of rats given a mixture of the three compounds. 3. Pharmacokinetic properties of the three compounds were determined in rats given the extracts of Da-Huang, Huang-Qin and Zhi-Zi. The pharmacokinetic parameters for emodin, baicalin and geniposide were found to be 0.13 ± 0.11, 0.25 ± 0.12 and 0.40 ± 0.09 h (Tmax); 21 ± 9, 1515 ± 254 and 482 ± 50 ng/mL (Cmax); 8.6 ± 5.5, 18.3 ± 2.8 and 22.1 ± 17.2 h (t1/2); 29 ± 20, 16886 ± 3734 and 2936 ± 551 ng/mLch (AUC(0-t)); and 37 ± 20, 22624 ± 6295 and 3582 ± 820 ng/mLch (AUC(0-∞)). 4. The metabolism and pharmacokinetic studies facilitate appropriate employment of Da-Huang, Huang-Qin and Zhi-Zi in clinic.

A sensitive LC-MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study.

Genipin (GP), an active metabolite of geniposide (GE), exhibits more potent pharmacological effects than its parent compound. In this paper, a sensitive LC-MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found that GP degraded rapidly in rat plasma at room temperature as a result of irreversible binding with the endogenous nucleophiles in plasma. GP was stable when the sample's pH was ≤4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions [M + CH3 COO]- m/z 447.3 → 225.3 for GE and [M - H]- m/z 225.2 → 123.1 for GP. The method exhibited high sensitivity (LLOQ 1 ng/mL for GE and 0.2 ng/mL for GP) by selecting the acetate adduct ions as the precursor ions for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.

Pharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in rats.

BACKGROUND: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. METHODS: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. RESULTS: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. CONCLUSION: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.

Evaluation of the Absorption Behavior of Main Component Compounds of Salt-Fried Herb Ingredients in Qing'e Pills by Using Caco-2 Cell Model.

Qing'e Pills is a Chinese traditional herbal product, which is often used to strengthen muscles and bones in TCM (traditional Chinese Medicine) practice. Its two main component herbs, namely, Cortex Eucommiae and Fructus Psoraleae are both required to be salt-fried according to TCM theory. We have evaluated the effects of salt-frying treated herbs on Caco-2 cell uptake behavior for those active ingredients of Qing'e Pills. By investigating of various variables, including MTT, temperature, inhibitors, pH, salt concentration and herb processing methods, we tried to clarify whether the salt-processing on herbs was necessary or not. Results showed that, compared to other processing methods, the salt-frying process significantly (p < 0.01) enhanced the absorption of effective components of Qing'e Pills. The way that psoralen, isopsoralen, psoralenoside and geniposide acid entered Caco-2 cells at low concentrations was via passive diffusion. These components were not substrates of P-glycoprotein. It demonstrated that the salt-frying process not only enhanced the concentration of active components in herb extract, but also changed their absorption behaviors. Nevertheless, the mechanism of absorption behavior changing needs to be further investigated.

Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method.

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r² > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the Cmax values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the Tmax and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein.

A Microdialysis in Adjuvant Arthritic Rats for Pharmacokinetics⁻Pharmacodynamics Modeling Study of Geniposide with Determination of Drug Concentration and Efficacy Levels in Dialysate.

Microdialysis, a sampling method for pharmacokinetics⁻pharmacodynamics (PK⁻PD) modeling in preclinical and clinical studies, is a convenient in vivo sampling technique. Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis fruit which has an anti-inflammatory effect. In this study, an articular cavity microdialysis sampling system for adjuvant arthritic (AA) rats was established to study the effect of GE on the release of prostaglandin E2 (PGE2) in AA rats induced by Freund's complete adjuvant (FCA). An UHPLC-MS/MS method was developed to determine the concentrations of GE and PGE2 in the dialysate. Through the determination of drug concentrations and PGE2 efficacy levels in the dialysate, the developed methods were successfully applied to set up concentration⁻time and effect⁻time profiles followed by PK⁻PD modeling of GE's effect on decreasing PGE2 release after oral administration of GE. The effect was well described by the developed PK⁻PD modeling, indicating that GE may play an anti-inflammatory role via decreasing AA-induced elevated PGE2 levels. In the selection of suitable endogenous small molecules as effect markers, the establishment of AA rat joint-cavity microdialysis is an attractive technique for rational PK⁻PD studies.

A Review on the Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Geniposide, a Natural Product.

Iridoid glycosides are natural products occurring widely in many herbal plants. Geniposide (C17H24O10) is a well-known one, present in nearly 40 species belonging to various families, especially the Rubiaceae. Along with this herbal component, dozens of its natural derivatives have also been isolated and characterized by researchers. Furthermore, a large body of pharmacological evidence has proved the various biological activities of geniposide, such as anti-inflammatory, anti-oxidative, anti-diabetic, neuroprotective, hepatoprotective, cholagogic effects and so on. However, there have been some research articles on its toxicity in recent years. Therefore, this review paper aims to provide the researchers with a comprehensive profile of geniposide on its phytochemistry, pharmacology, pharmacokinetics and toxicology in order to highlight some present issues and future perspectives as well as to help us develop and utilize this iridoid glycoside more efficiently and safely.

Study on the Absorption Mechanism of Geniposide in the Chinese Formula Huang-Lian-Jie-Du-Tang in Rats.

Huang-Lian-Jie-Du-Tang (HLJDT) is a classical recipe for relieving fever and toxicity for thousands of years in China. Geniposide is one of the main components in HLJDT. The present study was conducted in order to investigate the differences of absorption of geniposide after oral administration of geniposide alone and HLJDT in rats. Pharmacokinetic differences of geniposide following oral administrations of pure geniposide and HLJDT were investigated in vivo. The absorption of geniposide in pure compound and HLJDT was evaluated using intestinal perfusion and Caco-2 models. The in vivo and in vitro studies showed good relevance and consistent results. The co-occurring components in HLJDT were found to promote the absorption of geniposide from the pharmacokinetic study in vivo, intestinal perfusion, and Caco-2 model. Geniposide had better absorption in the duodenum and jejunum from the intestinal perfusion model, which was mainly absorbed by passive diffusion. Verapamil influenced the transportation of geniposide, while EDTA did not, demonstrating that geniposide might be the potential substance of P-glycoprotein in intestinal perfusion and Caco-2 models. The absorption of geniposide was studied systematically to guide the design of the oral dosage of geniposide and HLJDT in clinical therapy.

[Effect of wintergreen oil on in vitro transdermal permeation of osthole and geniposide].

The aim of this study was to investigate the transdermal penetration enhancement effect of wintergreen oil and its action mechanisms. The in vitro transdermal tests were carried out to study the transdermal penetration enhancement effect of wintergreen oil by using osthole and geniposide as the lipophilic and hydriphilic model drugs. Fourier-transform infrared spectroscopy was used to investigate the effect of wintergreen oil on the molecular structure of rat stratum corneum, and the scanning electron microscope was employed to observe the change of rat skin surface after treatment by the oil. The wintergreen oil at proper concentrations could effectively promote the transdermal permeation of osthole and geniposide, and exhibited better penetration-enhancing activity for the lipophilic osthole, close to the commonly used classical penetration enhancer azone. The infrared spectroscopy study and scanning electron microscope showed that wintergreen oil mainly acted on the stratum corneum lipids, reduced dense stratum corneum, and reduced the skin barrier function. Thus, the wintergreen oil could effectively facilitate the transdermal absorption of the lipophilic and hydrophilic drugs, resulting from the lowed skin barrier function.