Lignans from the genus Piper L. and their pharmacological activities: An updated review.

The genus Piper, a member of the Piperaceae family, comprises >2000 species, of which many are well known to possess considerable economic and medicinal values. Lignans are essential ingredients and are rich in Piper plants. Although many phytochemical studies have reported many lignans identified from Piper plants, comprehensive research has not reviewed these compounds. Hence, the present review reports on natural lignans from the genus Piper and their pharmacological activities. At least 275 lignans have been discovered from the Piper genus until October 2022, including traditional lignans, neolignans, oxyneolignans, norlignans, secolignans, and polyneolignans, especially some neolignans and norlignans with novel and complex scaffolds. In addition, these lignans have been reported to show various pharmacological activities, such as antimicrobial, anti-inflammatory, neuroprotective, antioxidative, anti-platelet aggregation, cytotoxic, anti-parasitic, CYP3A4 inhibitory activities, and so on. The current work presents an up-to-date critical review and a systematic summary of publications on lignans from the genus Piper to lay the groundwork and show better insights for further investigations.

[Research progress on intestinal microecology regulating mechanism and biological activities of polysaccharides].

Intestinal microecology is an important defense system in the human body. The intestinal flora is the core micro-ecosystem in the human intestine. It has a symbiotic relationship with the overall functions of the body. It has strong metabolic activity to maintain the normal functioning of the body and resist the invasion of various viral antigens in the body. Playing a protective function,the imbalanced intestinal microecology can cause various diseases. Polysaccharides can be extracted from a wide range of sources and have low toxicity and side effects. They have attracted wide attention because of their anti-tumor, anti-oxidant, anti-inflammatory and other biological activities. Studies have demonstrated that polysaccharides can regulate intestinal microecological disorders. According to the studies in recent years, this review summarizes that polysaccharides mainly modulate intestinal microecological disorders through regulating the composition of intestinal flora, improving the metabolism of the flora, and repairing the intestinal tract barrier. On the basis of these mechanisms of action, this paper elaborates the anti-tumor, immunomodulatory, and anti-inflammatory activities of polysaccharides. This paper can provide reference for the future research on the intestinal microecology-regulating mechanism and biological activities of polysaccharides.

[Research progress on mechanism of active ingredients in traditional Chinese medicine for gastric cancer].

Gastric cancer is a disease with high mortality, which threatens the health of people for a long time. At present, the main treatment methods are surgery and chemotherapy, but these methods have great harm to the human body. However, it is found that the active ingredients of traditional Chinese medicine have an obvious therapeutic effect in the adjuvant treatment of the tumor. Therefore, the active ingredients of traditional Chinese medicine have become a research hotspot in the anti-tumor field. In recent years, many related researchers have been particularly active in studying the in vitro activity and mechanism of active ingredients of traditional Chinese medicine on human gastric cancer cells. In this paper, the Chinese herbal medicine extracts, polysaccharides, alkaloids, saponins, flavones, terpenes, quinones, volatile oils, esters, phenols, protein components and other active ingredients of Chinese medicine were used as the starting points to investigate the anti-gastric cancer mechanism, such as inhibiting cell proliferation and inducing apoptosis of cancer cells, inhibiting cell invasion and migration; inhibiting over-expression of vascular endothelial growth factor(VEGF); interfering with cell mitosis; and regulating cell signaling pathways. Their in vitro inhibitory activity and mechanism for gastric cancer cells were described in this study, providing a theoretical reference for the development and application of anti-gastric cancer drugs.

[Research progress on anti-hepatocellular carcinoma mechanism of active ingredients of traditional Chinese medicine].

According to the latest data, the annual mortality rate of liver cancer in China ranks the second among malignant tumors, and it has become one of the most fatal cancers in urban and rural areas. This article starts with the active ingredients of traditional Chinese medicines for liver cancer to summarize the relevant literature at home and abroad, with the hope to provide theoretical references for the development of traditional Chinese medicines against liver cancer. The results show that the active ingredients of traditional Chinese medicines such as Chinese herbal extracts, flavonoids, polysaccharides, alkaloids, saponins, volatile oils, terpenes, quinones, phenols, bioenzymes, and protein components are the entry points, mainly by inhibiting the proliferation of cancer cells, blocking the cancer cell cycle, inhibiting the invasion and metastasis of cancer cells, regulating signal pathways, regulating vascular endothelial growth factor(VEGF) and reactive oxygen species(ROS), etc. to play the effects against liver cancer. It can be seen that the active ingredients of traditional Chinese medicine with coordinated intervention effects at multiple levels and multiple targets are expected to become ideal medicines for the treatment of liver cancer.

[Research progress in mechanism of traditional Chinese medicine active ingredients against cervical cancer].

Cervical cancer is the second cancer that threatens women' s health,and has attracted the attention of researchers at home and abroad because of its extremely high mortality rate. At present,most of the radiotherapy methods and chemical drugs for cancer treatment have serious side effects,and the active ingredients of traditional Chinese medicine have become the key research and development targets of anti-cancer drugs due to many advantages,such as multi-channel,multi-link,multi-target,and less toxicity. In recent years,researchers have been particularly active in researching the inhibitory activity and mechanism of active ingredients of traditional Chinese medicine for human cervical cancer cells. In this paper,the inhibitory activity and mechanism of traditional Chinese medicine against human cervical cancer cells were investigated from crude extract of traditional Chinese medicine,polysaccharides,alkaloids,saponins,flavonoids,terpenoids,quinones,volatile oils,esters,phenols,arsenical,protein components as the starting point; anti-cervical cancer mechanism was investigated,such as inhibiting cell proliferation inducing apoptosis of cancer cells,inhibiting cell invasion,migration and focal adhesion kinase( FAK) phosphorylation,inhibiting vascular endothelial growth factor( VEGF)over-expression interfering with cell mitosis,inhibiting Granzyme activity,regulating cellular signaling pathway,down-regulating HPV E6 gene expression,and regulating immune function. Its in vitro inhibitory activity and mechanism of action on cervical cancer cells were reviewed,in order to provide a theoretical basis for the development and utilization of anti-cervical cancer drugs.

Dual Engineering Interface-Driven Complementary Graphene Oxide-Protein Dimer Supramolecular Architecture Enables Nucleus Imaging and Therapy.

Seeking a versatile nanoplatform for multimodal nucleus imaging and therapy is a challenging task. General complementary bottom-up bionanotechnology for controlling a 3D supramolecular coassembly is proposed. The dual engineering interface proof-of-concept of the supramolecular architecture can be demonstrated via a genetically engineered protein dimer and plasmonically engineered graphene oxide (GO). Incorporation of anisotropic plasmonic nanoparticles as an intercalation layer among the GO 3D supramolecular architecture can provide covalent conjugation sites and simultaneously endow tunable optical properties of GO, ranging from the ultraviolet-to-near-infrared region. Interestingly, the precise design of a specific two-site mutation of the plasmid is favorable for giving an organized coassembly instead of random networks of GO, which contributes to giving continuous distinguishable enhanced Raman imaging for tracking cancer cells. Unexpectedly, penetration into the cell nucleus via the submicro 3D supramolecular coassembly exhibits an excellent nucleus therapeutic potential of cancer cells.

Quantification and efficient discovery of quality control markers for Emilia prenanthoidea DC. by Fingerprint-Efficacy Relationship Modelling.

An effective and comprehensive evaluation method for identifying the origin and assessing the quality of Emilia prenanthoidea DC. was established, based on analysis of high performance liquid chromatography (HPLC) fingerprint combined with the similarity analysis (SA), the hierarchical cluster analysis (HCA) and principal component analysis (PCA). Different data analysis methods drew a similar conclusion that 12 E. prenanthoidea (EP) samples were categorized into two groups. Evaluated the anti-inflammatory effects of different EP samples by analyzing paw edema (PE), serum superoxide dismutase (SOD) activity, concentrations of serum malondialdehyde (MDA), prostaglandin E2 (PGE2) and tumor necrosis factor α (TNF-α) in the carrageenin-induced acute inflammation mouse model. With the help of Gray Correlation Analysis (GRA), partial least squares regression (PLSR) and artificial neural network (ANN), the relationship between the fingerprints and efficacy of EP was elucidated. As the results, chlorogenic acid, hyperoside and quercitrin could be selected as chemical markers to evaluate the quality of EP from different regions. Thus, a method was established to quantify 7 major bioactive ingredients in the samples under the condition of fingerprint. These results indicated that the HPLC fingerprint coupleing with Profile-Efficacy analysis would have great has potential to identify the medicinal effective components and evaluating the quality of E. prenanthoidea.

UHPLC-ESI-MS/MS determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides Oliv extract.

This study aimed to develop a specific UHPLC-ESI-MS/MS method for simultaneous determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides. The chromatographic separation was achieved on a Hypersil GOLD column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 200 µL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring via an electrospray ionization source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with acetonitrile, and bergenin was used as internal standard. After oral administration of 3 mL/kg E. ulmoides extract in rats, the maximum plasma concentrations of pinoresinol glucoside and chlorogenic acid were 57.44 and 61.04 ng/mL, respectively. The times to reach the maximum plasma concentration were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic acid, respectively. The intra- and inter-day precision (RSD) values for the two analytes were <2.46 and 5.15%, respectively, and the accuracy (RE) values ranged from -12.76 to 0.00. This is the first study on pharmacokinetics of bioactive compounds in rat plasma after oral administration of E. ulmoides extract.

Optimized microwave-assistant extraction combined ultrasonic pretreatment of flavonoids from Periploca forrestii Schltr. and evaluation of its anti-allergic activity.

Microwave extraction combined ultrasonic pretreatment of flavonoids from Periploca forrestii Schltr. was investigated in this study, extraction process was first performed in an ultrasonic cleaner, then treated by microwave irradiation. The optimum ultrasonic time of 25 min was selected by single-factor experiments. A response surface methodology has been used to obtain a mathematical model that describes the process and analyzes the significant parameters ethanol concentration 59.92%, liquid to raw materials ratio 21.24 mL/g, microwave radiation time 209.53 s, and microwave power 274.14 w. In these optimum conditions, the yield of flavonoids from P. forrestii (TFPF) could be up to 9.11 ± 0.08%, which was increased by 14.30 and 19.86% compared microwave extraction and ultrasonic extraction, respectively. In vitro suppress hyaluronidase experimentation showed that TFPF purified using polyamide exhibited good anti-hyaluronidase ability with IC50 value of 1.033 mg/mL, possessing certain anti-antiallergic and potential application prospect in pharmaceutical production of treating inflammation and other related fields.

Relative tissue distribution and excretion studies of gastrodin and parishin from powder and extract of Gastrodiae Rhizoma in rat by UHPLC-ESI-MS/MS.

New research has indicated that Gastrodiae Rhizome (GR) has potential anti-diabetic and anti-asthmatic effects in mouse models. On the basis of our previous study of the relative bioavailability of gastrodin (GAS) and parishin (PA) from extract and powder of GR, we performed further research on the tissue distribution and excretion of the two analytes. A reliable bioanalytical method for the quantification of GAS and PA in rat tissues and excretion is required. Chromatographic separation was carried out on a gradient mobile phase of acetonitrile-water with 0.1% formic acid. Calibration curves (1/x2 weighted) offered satisfactory linearity (r2 > 0.9835) within 100-3000 ng mL-1 for GAS and (r2 > 0.9862) within 10-1000 ng mL-1 for PA. The relative standard deviations of the intra-day and inter-day precision were all <14.98%, whilst the relative errors of the intra-day and inter-day accuracy were all within ±14.71%. The matrix effect and recovery values were satisfactory in all of the biological matrices examination. The data of relative differences in tissue distribution and excretion of GAS and PA from powder and extract of GR indicated that higher bioavailabilities for GAS and PA were obtained when a dosage of 4 g kg-1 GR powder was used.

The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

Studies on Chromatographic Fingerprint and Fingerprinting Profile-Efficacy Relationship of Saxifraga stolonifera Meerb.

This work investigated the spectrum-effect relationships between high performance liquid chromatography (HPLC) fingerprints and the anti-benign prostatic hyperplasia activities of aqueous extracts from Saxifraga stolonifera. The fingerprints of S. stolonifera from various sources were established by HPLC and evaluated by similarity analysis (SA), hierarchical clustering analysis (HCA) and principal component analysis (PCA). Nine samples were obtained from these 24 batches of different origins, according to the results of SA, HCA and the common chromatographic peaks area. A testosterone-induced mouse model of benign prostatic hyperplasia (BPH) was used to establish the anti-benign prostatic hyperplasia activities of these nine S. stolonifera samples. The model was evaluated by analyzing prostatic index (PI), serum acid phosphatase (ACP) activity, concentrations of serum dihydrotestosterone (DHT), prostatic acid phosphatase (PACP) and type II 5α-reductase (SRD5A2). The spectrum-effect relationships between HPLC fingerprints and anti-benign prostatic hyperplasia activities were investigated using Grey Correlation Analysis (GRA) and partial least squares regression (PLSR). The results showed that a close correlation existed between the fingerprints and anti-benign prostatic hyperplasia activities, and peak 14 (chlorogenic acid), peak 17 (quercetin 5-O-ß-d-glucopyranoside) and peak 18 (quercetin 3-O-ß-l-rhamno-pyranoside) in the HPLC fingerprints might be the main active components against anti-benign prostatic hyperplasia. This work provides a general model for the study of spectrum-effect relationships of S. stolonifera by combing HPLC fingerprints with a testosterone-induced mouse model of BPH, which can be employed to discover the principle components of anti-benign prostatic hyperplasia bioactivity.

[Study on quality standard of Eucommia ulmoides based on absorbed active components in rat plasma].

The method was established for determination of geniposidic acid, chlorogenic acid, pinoresinoldiglucoside, which are three kinds of constituents of Eucommia ulmoides absorbed into the blood components. LC-MS/MS technique was applied to determine the blood components of the bloodstream after administration of E. ulmoides extract. At the same time, HPLC was used for detection of the ingredients content of the blood sample from 23 batches of E. ulmoides. The results showed that geniposidic acid, chlorogenic acid and pinoresinoldiglucoside are prototype into the blood in rats after oral administration of E. ulmoides extract, The linear range of geniposidic acid, chlorogenic acid and pinoresinoldiglucoside was good, and the average recoveries geniposidic acid, chlorogenic acid and pinoresinoldiglucoside were 98.69%, 100.8% and 98.39%, respectively. The method is simple and feasible with good reproducibility.

HPLC-DAD-ELSD Combined Pharmacodynamics and Serum Medicinal Chemistry for Quality Assessment of Huangqi Granule.

OBJECTIVE: To more scientifically and reasonably control the quality of Huangqi Granules, preliminary studies on the pharmacodynamics and serum pharmacochemistry of this medicine were performed. DPPH and MTT experiments showed that water extracts of Huangqi Granules had good antioxidant activity and increased immunity. Timed blood samples collected 5 min, 15 min, and 30 min after oral administration of a set amount of Huangqi Granules were collected and tested using UPLC-ESI-MS/MS. As a result, calycosin-7-O-ß-D-glucoside, ononin, calycosin, astragaloside IV, and formononetin were found to exist in rat blood after dosing, indicating that the five chemical compounds might have pharmacological activity, and based on this result, they were designated biomarkers for quality control of Huangqi Granules. Consequently, a simple, rapid and efficient method was developed in the present study for the simultaneous determination of the five characteristic compounds in Huangqi Granules using HPLC-DAD-ELSD. MATERIALS AND METHODS: The separation was performed using an Agilent Hypersil ODS column (4.6 × 250 mm, 5 µm) at 30 ℃. The mobile phase was composed of water (solvent A) and acetonitrile (solvent B) with a flow rate of 1 mL/min. The drift tube temperature of the ELSD system was set to 85 ℃, and the nitrogen pressure was 3.5 bar. RESULTS: All five characteristic compounds had good linear behavior with r2 values greater than 0.9972. The recoveries varied from 96.31% to 101.22%. Subsequently, the developed method was applied to evaluate the quality of Huangqi Granules from different batches, and hierarchical clustering analysis (HCA) was used to analyze the classification of the samples based on the values of the five compounds. CONCLUSION: The established HPLC method combined with HCA proved to be effective to evaluate the quality of Huangqi Granules.

A study of the geo-herbalism of evodiae fructus based on a flow-injection mass spectrometric fingerprinting method combined with chemometrics.

A flow-injection mass spectrometric (FIMS) fingerprinting method in combination with principal component analysis (PCA) was used to study the geo-herbalism of Evodiae Fructus (EF) samples. Twenty four EF samples from different regions in China were collected and analyzed. The PCA scores plot showed that the samples from Guizhou Province were scattered in different groups, however, most of the samples from other provinces were basically scattered in the same group. Nine characteristic compounds responsible for the classification of the samples were tentatively characterized. These nine compounds might help differentiating EF samples from different regions.

An UHPLC-MS/MS method for simultaneous quantification of gallic acid and protocatechuic acid in rat plasma after oral administration of Polygonum capitatum extract and its application to pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum capitatum Buch.-Ham. ex D. Don has been traditionally used by Hmong for the treatments of urinary tract infections and pyelonephritis. Gallic acid (GA) and protocatechuic acid (PCA) are regarded as two of the main bioactive compounds in the herb. MATERIALS AND METHODS: A rapid, selective and sensitive UHPLC-ESI-MS/MS method was established and validated for the quantification of GA and PCA in rat plasma after oral administration of P. capitatum extract. Concentrations of GA and PCA were determined at different time points after dosing 20 mg/kg (equivalent to 4 mg/kg of GA and 0.3 mg/kg of PCA), 60 mg/kg and 120 mg/kg of P. capitatum extract. The main pharmacokinetic parameters of GA and PCA were obtained based on the analysis of the plasma sample by non-compartmental analysis. RESULTS: After oral administration of P. capitatum extract, GA and PCA were quickly absorbed and showed a dose-dependent profile. Pharmacokinetic parameters for GA and PCA following oral administration of the extract were respectively: Cmax 246.24-806.27 and 15.73-30.72 ng/mL; Tmax 40-100 and 20-40 min. In the rats treated with P. capitatum t1/2 and Tmax of GA were prolonged by comparing with that of its pure form. CONCLUSION: Other compounds in P. capitatum extract may be metabolized to GA, which affected the pharmacokinetic profiles of GA. This pharmacokinetic study seems to be useful for a further clinical study of P. capitatum extract.

Relative bioavailability of gastrodin and parishin from extract and powder of Gastrodiae rhizoma in rat.

A rapid, sensitive and reliable UHPLC-ESI-MS/MS method was developed for simultaneous determination of gastrodin and parishin in rat plasma. The LLOQ of the two analytes were 1.00×10(-1) and 8.30×10(-5)µg/mL, respectively. The intra-day and inter-day precision were all less than 10% of the relative standard deviation (RSD), whilst the accuracy were all within ±15% of the relative error (RE). The proposed method was successfully applied for pharmacokinetics study on the two analytes in rats after oral administration of Gastrodiae rhizoma (GR) extract and powder at low, medium and high dosages. Blood samples were collected from the suborbital vein at predetermined time points and were precipitated using methanol. Chromatographic separations were carried out on a Kinetex XB-C18 column (2.1mm×150mm, 1.7µm) with a gradient mobile phase of acetonitrile-water with 0.1% formic acid as a modifier. The pharmacokinetic parameters of the two analytes in rats were obtained and the relative bioavailability of gastrodin and parishin in two formulations were calculated. The results indicated that higher bioavailability was obtained when low dosage of GR powder was used, whereas, higher bioavailability values were obtained when medium and high dosages of GR extract were used.

[Study on quality standard of Psammosilene tunicoides based on absorbed active components in rat plasma].

A method for determintion of allantion in Psammosilene tunicoides was established by HPLC. Using alcohol as the extraction solvent, the subsequent filtrate of P. tunicoides was analysed by HPLC. Allantoin was successfully detected and separated by ZORBAX NH2 column (4.6 mm x 150 mm,5 microm) at wavelength of 220 nm and column temperature of 40 degrees C, with acetonitrile-water (93: 7) as mobile phase at a flow rate of 1.0 mL x min(-1). The results showed that it had a good linear relationship between the concent ration of allantion and chromatographic peak area. The linear correlation coefficient of allantion was 0.999 5 in 0.010 4-0.166 g x L(-1). The relative standard deviation of six parallel injections was less than 2.1%. The average recoveries were ranged from 95.47% to 100.9%. This method was sensitive and accurate for the determination of allantion in P. tunicoides.

Studies on chromatographic fingerprint and fingerprinting profile-efficacy relationship of polygoni perfoliati herba.

Polygoni Perfoliati Herba is widely used in China with antibacterium, anti-inflammatory, expectorant, antitumor, and antivirus activities. To reveal the mechanisms of the activities of Polygoni Perfoliati Herba, the relationship between the fingerprinting profile and its bioactivities was investigated. In the present study, high-performance liquid chromatographic (HPLC) fingerprinting method was developed. The established method was applied to analyze 51 batches of Polygoni Perfoliati Herba samples collected from different locations or in different harvesting times in China. Chemometrics, including similarity analysis, hierarchical clustering analysis, and principal component analysis, were used to express their similarities. It was found that similarity values of the samples were in the range of 0.432-0.998. The results of analgesic tests indicated that Polygoni Perfoliati Herba could significantly inhibit pain induced by hot plate and acetic acid in mice. The results of anti-inflammatory tests showed that Polygoni Perfoliati Herba had good anti-inflammatory effects (P < 0.01) in two models including dimethyl benzene-induced ear edema and acetic acid-induced peritoneal permeability in mice. Combining the results from chromatographic fingerprints with those from bioactivities, we found that seven peaks from Polygoni Perfoliati Herba were mainly responsible for analgesic and anti-inflammatory activities.

[Chemical constituents from roots of Psammosilene tunicoides].

Three compounds, including a new one (1), were isolated from the roots of Psammosilene tunicoides. Based on analysis of NMR data as well as their physical and chemical properties, their structures were elucidated as 3,3'-(4,5-dimethoxynaphthalene-2,7-diyl) bis (1-nitropropan-1-one) (1), alpha-spinasterol-3-O-beta-D-glucopyranoside (2) and alpha-spinasteryl-3-O-beta-D-glucoside-6'-O-palmitate(3). Compounds 2 and 3 were isolated from this genus for the first time.