The extraction of active constituents from natural sources in a green and efficient manner is considered an important field in the pharmaceutical industry. In recent years, deep eutectic solvents ...(DESs), a new type of green solvent, have attracted increasing attention. Therefore, we aimed to establish a green and high-efficiency extraction method for ginsenosides based on DESs. This study takes Panax ginseng as a model sample. Eighteen different DESs were produced to extract polar ginsenosides. Ultrasound-assisted extraction (UAE) was applied for simplicity and efficiency. A binary DES synthesized using choline chloride and urea at a proportion of 1:2 prepared by a heating stirring method is proven to be more effective than other solvents, such as the widely used 70% ethanol for the extraction of ginsenosides. Three variables that might affect the extraction, including the DES content in the extraction solvent, liquid/solid ratio, and ultrasound extraction time, were evaluated for optimization. The optimum extraction conditions for ginsenosides were determined as follows: DES water content of 20 wt%, liquid/solid ratio of 15 mL g−1, and an ultrasonic extraction time of 15 min. The extraction yield for the optimized method is found to be 31% higher than that for 70% ethanol, which achieves efficient extraction. This study shows that DESs are available to extract ginsenosides for use in traditional Chinese medicine. The discovery also contributes to further research into the green extraction of ginsenosides.
Objective. Influenza virus poses a major threat to human health and has serious morbidity and mortality which commonly occurs in high-risk populations. Pharynx and larynx of the upper respiratory ...tract mucosa is the first defense line against influenza virus infection. However, the ability of the pharynx and larynx organ to eliminate the influenza pathogen is still not clear under different host conditions. Methods. In this study, a mouse model of kidney yang deficiency syndrome (KYDS) was used to mimic high-risk peoples. Two different methods of influenza A (H1N1) virus infection by nasal dropping or tracheal intubation were applied to these mice, which were divided into four groups: normal intubation (NI) group, normal nasal dropping (ND) group, model intubation (MI) group, and model nasal dropping (MD) group. The normal control (NC) group was used as a negative control. Body weight, rectal temperature, and survival rate were observed every day. Histopathologic changes, visceral index, gene expressions of H1N1, cytokine expressions, secretory IgA (SIgA) antibodies of tracheal lavage fluids in the upper respiratory tract, and bronchoalveolar lavage fluids were analyzed by ELISA. Results. The MD group had an earlier serious morbidity and mortality than the others. MI and NI groups became severe only in the 6th to 7th day after infection. The index of the lung increased significantly in NI, MI, and MD groups. Conversely, indices of the thymus and spleen increased significantly in NC and ND groups. H&E staining showed severe tissue lesions in MD, MI, and NI groups. H1N1 gene expressions were higher in the MD group compared with the MI group on the 3rd day; however, the MD group decreased significantly on the 7th day. IL-6 levels increased remarkably, and SIgA expressions decreased significantly in the MD group compared with the NC group. Conclusions. SIgA secretions are influenced directly by different conditions of the host in the pharynx and larynx in the upper respiratory tract mucosa. In the KYDS virus disease mode, SIgA expressions could be inhibited severely, which leads to serious morbidity and mortality after influenza A virus infection. The SIgA expressions of the pharynx and larynx would be an important target in high-risk populations against the influenza A virus for vaccine or antiviral drugs research.
ETHNOPHARMACOLOGICAL RELEVANCEBorneol (BO) represents a global trade-driven spreading of ethnic medicine traceable to the classical age, and won its name specific to its original habitat "Borneo". BO ...shows broad spectral pharmacological effects, such as anti-inflammatory, analgesic, antipyretic, inducing resuscitation, and widely applied in the protection and treatment of cardiovascular and cerebrovascular diseases, used singly or mostly in compound formulae. AIM OF THE STUDYThree stereoscopic configuration forms of BO, l-borneol (LB), d-borneol (DB), and dl-borneol (synthetic, SB), are formulated in broad spectral application, yet their diverse pharmacodynamic and pharmacokinetic properties caused by configurations, and accurate assay and quality assessment are often overlooked. A systematic review and analysis of lumped studies and applications is necessary to clarify the relationship between configuration and its original plant, analysis method, activity and side effect BO in order to guarantee the efficacy and safety during their application. MATERIALS AND METHODSThe public databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure were referenced to summarize a comprehensive research and application data of BO published up to date. RESULTSThis review includes following sections: History and current status, Stereochemistry, Ethnopharmacology, and Quality assessment. In the section of history, the changes of the plant origins of the two isomeric forms of natural BO were described respectively, and the methods for synthetic racemate SB were also included. The section of stereochemistry deals with the stereoscopic structures, physical/chemical property, optical rotation of the three forms of BO, as well as the main related substances like isoborneol, obtained in SB via chemical transformation of camphor and turpentine oil. In the section of Ethnopharmacology, pharmacological activities and pharmacokinetics of different forms of BO were discussed. BO is usually used as an "adjuvant", by enhancing the permeability of the blood-brain barrier and intervene the ADME/T pathways of the other ingredients in the same formulation. In the section of quality assessment, the analytical methods, including chromatography, especially GC, and spectroscopy were addressed on the chiral separation of the coexisting enantiomers. CONCLUSIONSThis overview systematically summarized three forms of BO in terms of history, stereochemistry, ethnopharmacology, and quality assessment, which, hopefully, can provide valuable information and strategy for more reasonable application and development of the globally reputed ethnic medicine borneol with characteristics in stereochemistry.
Panax notoginseng (Burk.) F. H. Chen, a valuable Chinese herb medicine, shows a characteristic bi-directional regulation of hemostasis and activating blood circulation with ginsenosides as the ...predominant bioactive compounds and is a typical representative of “processing triggered heteropotency”.
Processing triggered heteropotency, one of the unique theories and practices in traditional Chinese medicine, refers to that the processing will lead to change in physical and chemical properties, and eventually disparate efficacy of the crude drugs, yet the optimum process and underlying mechanism remains unclear. In this study, using Panax notoginseng (PN) as a representative sample, a processing-(chemical) profiling-pharmacodynamics (3-P) relationship was proposed to investigate the processing mechanism of PN.
Firstly, a temperature programmed steaming process was designed to evaluate the steaming triggered chemical transformation of triterpene saponins and the corresponding enhancement in anti-platelet aggregation activity. The steaming process was programed from the conventional 100 °C–150 °C in a time course of 0–12 h, aiming to achieve the maximized conversion of rare ginsenosides (RGs), and dynamic profile of ginsenosides were constructed by a UPLC-Q-TOF-MS/MS analysis. Then, a processing-(chemical) profiling-pharmacodynamics (3-P) relationship was assessed by using the grey relational analysis (GRA) and orthogonal projections to latent structures (OPLS), and validated by bioactive fraction of 140 °C steamed PN. Subsequently, the P2Y12-ligand binding affinity of potential candidates was analyzed by molecular docking. Finally, the dynamic changes of ginsenosides during steaming of SPN were quantitatively detected by UPLC-QQQ-MS/MS.
A total of 48 differential ginsenosides were characterized and monitored including the primary and secondarily transformed saponins. The higher temperature steaming especially at 140 °C induces not only the predominant production of the RGs, but also the stronger anti-platelet aggregation activity. The 3-P relationship showed the fraction (3) of 140 °C steamed PN rich in RGs exhibits the most predominant efficacy, in which, a series of RGs including ginsenosides Rg5, Rk1, 20(S/R)-Rg3 were proven to be potent components. Molecular docking analysis suggested that ginsenosides Rg5 and Rk1 showed more strong interaction with the platelet P2Y12 receptor. Quantitative analysis found 140 °C-2h PN possessed highest contents of Rk1 and Rg5 and total RGs.
The integrated 3-P strategy uncovered the promising ginsenosides with anti-platelet effect, thereby revealing the material basis of PN steaming, which could provide a new enlightenment for the investigation of processing mechanism of traditional Chinese medicines.
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•A versatile economic strategy was proposed for SMF research.•A high-throughput CAD method for 50 compounds characterization was established.•This method showed potency to distinguish the ...authenticity of raw materials used in Shengmai preparations.•Components transferring information of SMF from raw materials to preparations were revealed, which can guide the quality improvement of SMF.
Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost.
We aimed to establish a versatile analysis strategy using HPLC–CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations.
By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established.
In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations.
The established versatile analysis strategy based on HPLC–CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.
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Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng, shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an ...adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards.
This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios.
In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios.
The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d-borneol (DB), l-borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine.
This study shed new light on the compatible use of PNS and BO from the perspective of “configuration-dose-influence” of BO. The results provide important basis for the clinical application and selection of BO.
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•Borneol (BO) promoted the oral absorption of Panax notoginseng saponins (PNS) in rat.•Dl-borneol (synthetic) increased PNS exposure in rats more than d- or l-borneol.•Compatibility ratio of BO and PNS at 1:1 can better promote the absorption of PNS.
Obesity has emerged as a worldwide metabolic disease, given its rapid growth in global prevalence. Red ginseng extracts (RGS), one of the traditional processed products of ginseng, show the potential ...to improve the metabolic phenotype of obesity. However, the RGS mechanism for regulating obesity and late insulin resistance remains to be clarified.
This study aimed to emphasize the potential use of RGS in treatment of obesity and insulin resistance (IR) and explore the underlying mechanism affecting glucose and lipid metabolism improvements.
The role of RGS was evaluated in a high-fat diet (HFD) rodent model. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to characterize the glucose metabolism level. The expression of lipolysis proteins and uncoupling protein-1 (UCP-1) were investigated by western blot. Glucagon-like peptide-1 (GLP-1) and apical sodium-dependent bile acid transporter (ASBT) protein expression in the intestine were determined via immunofluorescence. UPLC-Q-TOF-MS were used to detect the alterations in bile acids (BAs) levels in serum, ileum, and inguinal white adipose tissue (iWAT). In addition, intestine-specific Tgr5 knockout mice were employed to verify the efficacy of RGS in improving obesity.
RGS treatment alleviated dietary-induced dyslipidemia and IR in obese mice in a dose-dependent manner and improved glucose and insulin tolerance, and energy expenditure. RGS treatment significantly reduced lipid deposition and induced GLP-1 secretion in the intestine of wild-type mice but not in Tgr5ΔIN obese mice. Furthermore, RGS intervention increased BA levels in serum, ileum, and iWAT. The increase of circulating BAs in mice was related to the activation of ileal TGR5 and the promotion of ASBT translocation to the plasma membrane, thus affecting BA transport. Next, the increased level of circulating BAs entered the periphery, which might facilitate lipolysis and energy consumption by activating TGR5 in iWAT.
Our results demonstrated that RGS significantly alleviated HFD-induced obesity and insulin resistance in mice. RGS intervention improved glucose metabolism, promoted lipolysis, and energy metabolism by activating TGR5 in the intestine. In addition, we found that activating intestinal TGR5 facilitated the localization of ASBT to the plasma membrane, which ultimately promoted the transport of BAs to regulate metabolic phenotype.
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•Rare ginsenosides (RGs), as the shining components, possessed great potential in drugs and nutraceuticals.•A total of 144 rare ginsenosides with diverse skeletons and bioactivities ...were isolated from Panax species.•RGs showed superior bioactivity for CVDs and cancer, and they acted as natural ligands for some specific receptors.•The stereochemistry properties of RGs brought out diverse bioactivities and novel analytical strategies.•Physico-chemical transformation, biotransformation, and biosynthesis for RGs are summarized.
Rare ginsenosides (Rg3, Rh2, C-K, etc.) refer to a group of dammarane triterpenoids that exist in low natural abundance, mostly produced by deglycosylation or side chain modification via physicochemical processing or metabolic transformation in gut, and last but not least, exhibited potent biological activity comparing to the primary ginsenosides, which lead to a high concern in both the research and development of ginseng and ginsenoside-related nutraceutical and natural products. Nevertheless, a comprehensive review on these promising compounds is not available yet.
In this review, recent advances of Rare ginsenosides (RGs) were summarized dealing with the structurally diverse characteristics, traditional usage, drug discovery situation, clinical application, pharmacological effects and the underlying mechanisms, structure–activity relationship, toxicity, the stereochemistry properties, and production strategies.
A total of 144 RGs with diverse skeletons and bioactivities were isolated from Panax species. RGs acted as natural ligands on some specific receptors, such as bile acid receptors, steroid hormone receptors, and adenosine diphosphate (ADP) receptors. The RGs showed promising bioactivities including immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes, and interaction with gut microbiota. Clinical trials indicated the potential of RGs, while high quality data remains inadequate, and no obvious side effects was found. The stereochemistry properties induced by deglycosylation at C (20) were also addressed including pharmacodynamics behaviors, together with the state-of-art analytical strategies for the identification of saponin stereoisomers. Finally, the batch preparation of targeted RGs by designated strategies including heating or acid/ alkaline-assisted processes, and enzymatic biotransformation and biosynthesis were discussed. Hopefully, the present review can provide more clues for the extensive understanding and future in-depth research and development of RGs, originated from the worldwide well recognized ginseng plants.
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