Arctigenin from Fructus arctii Exhibits Antiaging Effects via Autophagy Induction, Antioxidative Stress, and Increase in Telomerase Activity in Yeast.

Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called "senomorphics". In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future.

Chromatographic fingerprint combined with quantitative analysis of multi-components by single-marker for quality control of total lignans from Fructus arctii by high-performance liquid chromatography.

INTRODUCTION: The total lignans from Fructus arctii (TLFA) is a mixture of a series of lignans isolated from dried ripe fruit of Arctium lappa L. We previously reported on the pharmacological activity of TLFA that is related to diabetes. An accurate and practical TLFA quantitative analysis method for utilising it needs to be established. OBJECTIVE: This study aimed to develop an effective quantitative analysis method for assessing the TLFA quality. METHODS: A total of 11 marker components were confirmed by analysing the high-performance liquid chromatography fingerprints of 24 batches of TLFA samples. The samples were prepared from TLFA and structurally identified as lappaol H, lappaol C, arctiin, arctignan D, arctignan E, matairesinol, arctignan G, isolappaol A, lappaol A, arctigenin, and lappaol F. In the quantitative analysis of multi-components by the single-marker (QAMS) method and with arctiin as an internal reference substance, the content of these lignans in TLFA was simultaneously determined according to their relative correction factors with arctiin. RESULTS: There was no significant difference between results measured by the QAMS and traditional external standard methods. Hierarchical cluster and principal component analyses were performed to evaluate 24 TLFA batches based on the contents of 10 marker components. The results revealed that QAMS method combined with chemometric analyses could accurately measure and clearly distinguish the different quality samples of TLFA. CONCLUSION: The QAMS method is a reliable and promising quality control method for TLFA. It can provide a reference for promoting quality control of complex multi-component systems, especially for traditional Chinese medicine.

Fructus arctii: an overview on its traditional uses, pharmacology and phytochemistry.

OBJECTIVES: Fructus arctii (F. arctii) is the dried ripe fruit of Arctium lappa Willd (Asteraceae). It is being used as a traditional medicine in China, Japan, Iran, Europe, Afghanistan, India, etc. for cough, inflammation, clearing the heat, detoxification, cancer and diabetes. This review summarized the botanical description, distribution, ethnopharmacology, bioactive constituents and pharmacological actions of F. arctii including methods to assess its quality. In addition, this review also provides insights into future research directions on F. arctii to further explore its bioactive constituents, mechanism involved in pharmacological activity, and clinical use including the development of new analytical methods for assessing the quality. KEY FINDINGS: The comprehensive analysis of the literature revealed that F. arctii contains lignans, volatile oil, flavonoids, sesquiterpenoids, triterpenes, phenolic acids, etc. Experimental studies on various extracts and drug formulations showed that it has antioxidant, antimicrobial, hypoglycaemic, lipid-lowering, anti-inflammatory, analgesic, antiviral, anti-tumour activity, etc. SUMMARY: The pharmacological activity of a few major constituents in F. arctii have been identified. However, there are still need more studies and more new technologies to prove the pharmacological activity and the effective mechanism of the other constituents that undergoing uncertain. Except for the animal experiments, clinical studies should be carried out to provide the evidence for clinical application.

Optimisation of the Conversion and Extraction of Arctigenin From Fructus arctii Into Arctiin Using Fungi.

Fructus arctii is commonly used in Chinese medicine, and arctiin and arctigenin are its main active ingredients. Arctiin has low bioavailability in the human body and needs to be converted into arctigenin by intestinal microbes before it can be absorbed into the blood. Arctigenin has antiviral, anti-inflammatory, and anti-tumour effects and its development has important value. In this study, we used external microbial fermentation with Aspergillus awamori and Trichoderma reesei to process and convert arctiin from F. arctii powder into arctigenin, hence increasing its bioavailability. We developed a fermentation process by optimising the carbon and nitrogen source/ratio, fermentation time, pH, liquid volume, inoculation volume, and substrate solid-liquid ratio. This allowed for an arctiin conversion rate of 99.84%, and the dissolution rate of the final product was 95.74%, with a loss rate as low as 4.26%. After the fermentation of F. arctii powder, the average yield of arctigenin is 19.51 mg/g. Crude fermented F. arctii extract was purified by silica gel column chromatography, and we observed an arctigenin purity of 99.33%. Our technique effectively converts arctiin and extracts arctigenin from F. arctii and provides a solid basis for further development and industrialisation.

An integrated strategy for revealing the pharmacological changes based on metabolites profiling and network pharmacology: Arctiin as an example.

Traditional Chinese medicine was widely used in China since its definite effects and therapy. The components of TCM were absorbed into the circle system as the format of prototypes or metabolites, which contributed to the therapy or side effects. Declaring the functional changes in this process was of great importance to the clinical applications. In this work, an integrated strategy based on metabolites' profiling and network pharmacology was proposed for exploring the pharmacological changes of compounds in vivo. Arctiin, the main component in Fructus Arctii with various kinds of bioactivities, was used as an example. An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry and metabolynx™software was applied to characterize the metabolites of arctiin in rats at a dosage of 100 mg/kg; network pharmacology was applied to characterize the functional changes. As a result, fifty-three metabolites (32 in plasma, 40 in urine, 19 in bile, 20 in feces, 1 in brain, 12 in liver and 4 in lungs) were screened out and characterized, and 3 of them were unambitiously identified by comparison with standard substances. Among them, 38 metabolites were reported for the first time. It was found the major metabolic pathways of arctiin in rats were demethylation, lactone-opening and phase II conjugations with sulfate and glucuronide.It also confirmed that M14, M15, M18, M23, M22, M43 and M45 were the major circulating forms of arctiin in rats following oral administration. In addition to the above metabolic reactions, phase I reactions of hydrolysis, demethylation, dehydroxylation were also observed, and dehydrogenation were first revealed metabolic patterns of arctiin in rats. Meanwhile, in addition to the main targets of arctiin (MTOR, EGFR and MAPK14), its metabolites targeted additional 392 targets with additional functions of anti-hepatitis B or viral carcinogenesis (SRC, CAPS3, PIK3CA, CDK4, ESR1, MMP9 and ERBB2). The above results provided very important information for understanding the metabolism and functional changes of arctiinin vivo, and supporting data for further pharmacological evaluation. Our work also provided a newsight for elucidation of functional changes of TCMs in vivo.

The effect of total lignans from Fructus Arctii on Streptozotocin-induced diabetic retinopathy in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Arctii is the dried ripe fruit of Arctium lappa L. (family Asteraceae). It is a well-known Chinese Materia Medica that was included in the Chinese pharmacopoeia because of its traditional therapeutic actions, such as heat removal, detoxification, and elimination of swelling. Since ancient times Fructus Arctii has been used extensively in a number of classical drug formulas to treat type 2 diabetes mellitus. Modern pharmacological studies have shown that certain components of Fructus Arctii have multiple physiological activities on type 2 diabetes and its complications. AIM OF THE STUDY: We have reported the inhibitory effect of total lignans from Fructus Arctii (TLFA) on aldose reductase, the key enzyme in the polyol pathway, which is considered to be closely related to the onset of diabetic retinopathy (DR). The present study aimed to observe the preventive and therapeutic effects of TLFA on DR in Streptozotocin (STZ)-induced DR rats. MATERIALS AND METHODS: TLFA was prepared from Fructus Arctii and its content was determined using UV spectrophotometry. The DR model was induced by STZ in Wistar rats. For DR prevention, the animals were gavaged once daily for 9 weeks with TLFA (1.38, 0.69, and 0.35 g/kg/day) as soon as they were confirmed as diabetes models. Pathological changes to retinal tissues and the expression of vascular endothelial growth factor (VEGF) and protein kinase C (PKC) in the retina were detected after TLFA treatment. The effects of TLFA on blood glucose levels and body weight were also observed. For DR treatment, the animals were gavaged once daily for 12 weeks with TLFA (1.38 and 0.69 g/kg/day) at 3 months after they were confirmed as diabetes models. The therapeutic effect was studied using quantitative detection of blood-retina barrier (BRB) breakdown via an Evans Blue leakage assay. RESULTS: For DR prevention, after 9 weeks of TLFA administration, histopathological examination of retinal tissue showed that TLFA improved the lesions in the retina. Changes to retinal microstructures such as capillaries, ganglion cells, bipolar cells, and the membrane disk examined by electron microscopy further confirmed that TLFA has a preventive effect on retinopathy. Terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) detection showed that TLFA could inhibit retinal cell apoptosis in the diabetic rats, and fasting blood glucose (FBG) levels of rats in the TLFA-treated groups decreased during the experiment. For DR treatment, after 3 months of administration, the amount of dye leakage in the TLFA-administered groups was reduced by more than 50% compared with that in the model group, which indicated that TLFA has a therapeutic effect on middle and late DR. Messenger RNA (mRNA) expression of VEGF and PKCß2 in the retina detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) showed that TLFA could inhibit the expression of them, which was consistent with the results of immunohistochemistry (IHC). CONCLUSION: TLFA has a preventive and therapeutic effect on DR. Its mechanism of action on DR is related to inhibiting PKC activation and blocking VEGF elevation.

Pharmacokinetics of Arctigenin and Fructus Arctii Powder in Piglets.

Fructus arctii, also known as great power seed, is the dried fruit of Arctium lappa of the family Compositae. It is a commonly used veterinary herbal medicine, and arctigenin is the main active ingredient. The aim of this study was to characterize the absorption, distribution, metabolism, and excretion of arctigenin and Fructus arctii powder in piglets. These data were used to provide a theoretical reference for the development and clinical use of new veterinary drugs. Sixteen healthy piglets (mean weight 30.0 ± 5.0 kg) were divided into two groups. One group was administered 2.0 mg/kg body weight (bw) arctigenin intravenously, and the other was administered 1.0 g/kg.bw Fructus arctii powder by gavage. Blood samples were collected from the anterior vena cava at different time points, and the concentration of arctigenin in the plasma of the piglets was determined using high-performance liquid chromatography (HPLC). Arctigenin conformed to a two-compartment model with no absorption, and the main pharmacokinetic parameters were as follows: distribution half-life (t 1/2α)-0.166 ± 0.022 h; elimination half-life (t 1/2ß)-3.161 ± 0.296 h; apparent volume of distribution (V d)-0.231 ± 0.033 L/kg; clearance rate (CLb)-0.057 ± 0.003 L/(h.kg); and area under the curve (AUC)-1.189 ± 0.057 g.h/mL. The pharmacokinetic parameters of arctigenin following oral administration of the Fructus arctii powder were as follows: absorption half-life (t 1/2ka)-0.274 ± 0.102 h, t 1/2α-1.435 ± 0.725 h, t 1/2ß-63.467 ± 29.115 h, V d-1.680 ± 0.402 L/kg, CLb-0.076 ± 0.028 L/(h kg), peak time (t max)-0.853 ± 0.211 h, peak concentration (C max)-0.430 ± 0.035 g/mL, and AUC-14.672 ± 4.813 g/mL. These results indicated that intravenous arctigenin was sparingly distributed in tissues. In contrast, orally administered Fructus arctii powder was rapidly absorbed, more widely distributed, and more slowly eliminated than the intravenous arctigenin, which may indicate its sustained pharmacological effects.

[Study on high throughput sequencing identification of Fructus Arctii and five counterfeit species mix power].

Fructus Arctii is a traditional Chinese medicine. The main counterfeit species are the seeds of Arctium tomentosum, Onopordum acanthium, Silybum marianum, Saussurea costus, Amorpha fruticosa. Traditional identification methods or molecular barcoding techniques can identify Fructus Arctii and its counterfeit species. However, the identification of the mixture of it and its spurious species is rarely reported. In this paper, we sequenced the ITS2 sequences of Fructus Arctii and 5 kinds of spurious species mix powder by high-throughput sequencing to identify the mixed powder species and providing new ideas for the identification of Fructus Arctii mix powder. The total DNA in mixed powder was extracted, and the ITS2 sequences in total DNA was amplified. Paired-end sequencing was performed on the DNA fragment of the community using the Illumina MiSeq platform. The sequence was analyzed by the software FLASH, QIIME and GraPhlAn etc. The results showed that the high quality ITS2 sequences of 39910 mix samples were obtained from the mixed samples, of which the total ITS2 sequence of the samples genus was 34 935. Phylogenetic analysis showed that the samples contained Fructus Arctii, A. tomentosum, O. acanthium, S. marianum, S. costus and A. fruticosa. Using ITS2 sequences as DNA barcodes, high-throughput sequencing technology can be used to detect the Fructus Arctii and its spurious specie in mixed powder, which can provide reference for the quality control, safe use of medicinal materials of Fructus Arctii and the identification of mixed powder of traditional Chinese medicine.

Novel Method of Preparation and Activity Research on Arctigenin from Fructus Arctii.

BACKGROUND: Arctigenin has many pharmacological activities with clinical significance and is derived from Arctium lappa L. However, the present extraction method is inefficient and does not have meaningful industrial production. OBJECTIVE: A new method to directly prepare arctigenin was established by combining enzyme-assisted extraction and central composite design. Arctigenin's further pharmacological activity was also surveyed in vitro. MATERIALS AND METHODS: ß-D-Glucosidase, a food-grade enzyme, was added directly to the fruits of A. lappa L. to hydrolyze the arctiin to arctigenin, and the obtained samples were subsequently subjected to ethanol (30%, v/v) extraction. The pharmacological activity of the extraction and arctigenin was determined by inhibiting acetylcholinesterase (AChE) and scavenging nitrite. RESULTS: The factors investigated include the enzyme concentration (0.5%-2.5%), ultrasound time (10 min-3 0 min), and extraction temperature (30°C-50°C). From the analysis of the results by Design-Expert (V8.0.6), the optimal extraction conditions were obtained: enzyme concentration (1.4%), ultrasound time (25 min), and extraction temperature (45°C). The highest yield of arctigenin, obtained under the optimal conditions was 6.39%, representing an increase of 28.15% compared to the reference extraction without enzyme processing. The IC50 values of the extraction and arctigenin, respectively, for inhibiting AChE were 0.572 mg/ml and 0.462 mg/ml, and those for nitrite-scavenging were 34.571 mg/ml and 17.49 mg/ml. CONCLUSIONS: The results demonstrate that using an enzyme directly in the production is an effective means for extracting arctigenin from Fructus arctii. The extraction has the activities of inhibiting AChE and scavenging nitrite, probably because there has arctigenin in it. It is implied that the extraction and arctigenin could contribute to human health in clinical applications. SUMMARY: The new method of adding enzyme directly to the preparation of arctigenin was carried out instead of preparing arctigenin by two-step methodThree factors affecting the efficiency of preparation were analyzed and discussed include the enzyme concentration, ultrasound time, and extraction temperature by central composite designThis new method of preparing arctigenin improved the yield significantly than other methodsArctigenin has remarkable pharmacological activities of inhibiting acetylcholinesterase and scavenging nitrite. Abbreviations used: AChE: Acetylcholinesterase, CCD: Central composite design, TCM: Traditional Chinese medicines, AD.

The effects of hypoglycemia and weight loss of total lignans from Fructus Arctii in KKAy mice and its mechanisms of the activity.

Fructus Arctii (great burdock achene) is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is included in the Chinese pharmacopoeia. It has been reported that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. This study aimed to investigate antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous Type 2 diabetic rodent model that exhibits marked obesity. In this study, KKAy mice were gavaged once daily with solvents (0.5% sodium carboxymethyl cellulose), TLFA (250 and 125 mg/kg), or metformin (200 mg/kg) for 11 weeks, and C57BL/6J mice treated with saline solution (0.9%, w/v) were used as normal control. The results indicate that TLFA has dual effects of hypoglycemia and weight loss, and administration of TLFA in KKAy mice could decrease fasting blood glucose, glycated hemoglobin, and body weight; improve oral glucose tolerance; increase high density lipoprotein cholesterol; and decrease triglycerides and free fatty acid in mice serum. Its efficacy may associate with multiple mechanisms of action such as stimulation of insulin secretion, activation of phosphatidylinositol 3-kinase/protein kinase B, and adenosine-monophosphate-activated protein kinase signaling pathway, decreasing leptin.

Study on high throughput sequencing identification of Fructus Arctii and five counterfeit species mix power / 中国中药杂志

Fructus Arctii is a traditional Chinese medicine. The main counterfeit species are the seeds of Arctium tomentosum, Onopordum acanthium, Silybum marianum, Saussurea costus, Amorpha fruticosa. Traditional identification methods or molecular barcoding techniques can identify Fructus Arctii and its counterfeit species. However, the identification of the mixture of it and its spurious species is rarely reported. In this paper, we sequenced the ITS2 sequences of Fructus Arctii and 5 kinds of spurious species mix powder by high-throughput sequencing to identify the mixed powder species and providing new ideas for the identification of Fructus Arctii mix powder. The total DNA in mixed powder was extracted, and the ITS2 sequences in total DNA was amplified. Paired-end sequencing was performed on the DNA fragment of the community using the Illumina MiSeq platform. The sequence was analyzed by the software FLASH, QIIME and GraPhlAn etc. The results showed that the high quality ITS2 sequences of 39910 mix samples were obtained from the mixed samples, of which the total ITS2 sequence of the samples genus was 34 935. Phylogenetic analysis showed that the samples contained Fructus Arctii, A. tomentosum, O. acanthium, S. marianum, S. costus and A. fruticosa. Using ITS2 sequences as DNA barcodes, high-throughput sequencing technology can be used to detect the Fructus Arctii and its spurious specie in mixed powder, which can provide reference for the quality control, safe use of medicinal materials of Fructus Arctii and the identification of mixed powder of traditional Chinese medicine.

Qualitative and quantitative analysis of major constituents of raw and processed Arctii Fructus by UHPLC-UV-Q-TOF-MS/MS / 药学学报

In this study, we developed a qualitative analytical method based on liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) for identification of multi-constituents of raw Fructus Arctii (RFA) and processed Fructus Arctii (PFA). We established a UHPLC-UV analytical method for simultaneously determining 6 major compounds in Fructus Arctii. UHPLC- Q-TOF-MS/MS qualitative analysis was performed under negative and positive ion modes and a total of 23 chemical compounds were identified. The analysis data were subjected to a principle component analysis with a t-test. Ten peaks were found to be the main difference (P<0.05) between RFA and PFA. HPLC-UV quantitative method result showed the contents of 6 constituents were different between RFA and PFA. The results indicated that there was less arctiin, chlorogenic acid, isochlorogenic acid A in PFA than in RFA. However, there were higher levels of arctigenin, isochlorogenic acid B, isochlorogenic acid C in the PFA than RFA, which may be the main reason for different clinical efficacy of RFA and PFA.

Optimization of the processing technology of Fructus Arctii by response surface methodology.

The present study was designed to optimize the processing of Fructus Arctii by response surface methodology (RSM). Based on single factor studies, a three-variable, three-level Box-Behnken design (BBD) was used to monitor the effects of independent variables, including processing temperature and time, on the dependent variables. Response surfaces and contour plots of the contents of total lignans, chlorogenic acid, arctiin, and arctigenin were obtained through ultraviolet and visible (UV-Vis) monitoring and high performance liquid chromatography (HPLC). Fructus Arctii should be processed under heating in a pot at 311 °C, medicine at 119 °C for 123s with flipping frequently. The experimental values under the optimized processing technology were consistent with the predicted values. In conclusion, RSM is an effective method to optimize the processing of traditional Chinese medicine (TCM).

Arctigenic acid, the key substance responsible for the hypoglycemic activity of Fructus Arctii.

We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively. GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice. This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.

Quality assessment of raw and processed Arctium lappa L. through multicomponent quantification, chromatographic fingerprint, and related chemometric analysis.

In traditional Chinese medicine, raw and processed herbs are used to treat different diseases. Suitable quality assessment methods are crucial for the discrimination between raw and processed herbs. The dried fruit of Arctium lappa L. and their processed products are widely used in traditional Chinese medicine, yet their therapeutic effects are different. In this study, a novel strategy using high-performance liquid chromatography and diode array detection coupled with multivariate statistical analysis to rapidly explore raw and processed Arctium lappa L. was proposed and validated. Four main components in a total of 30 batches of raw and processed Fructus Arctii samples were analyzed, and ten characteristic peaks were identified in the fingerprint common pattern. Furthermore, similarity evaluation, principal component analysis, and hierachical cluster analysis were applied to demonstrate the distinction. The results suggested that the relative amounts of the chemical components of raw and processed Fructus Arctii samples are different. This new method has been successfully applied to detect the raw and processed Fructus Arctii in marketed herbal medicinal products.

Study on the Quality Standard of Fructus arctii Concentrated Granules / 中国药房

OBJECTIVE:To establish the quality standard of Fructus arctii concentrated granules. METHODS:TLC was con-ducted for the qualitative identification and HPLC was used for the content determination of arctiin in F. arctii concentrated gran-ules. The determination was performed on Dionex C18 column with mobile phase consisted of methanol-water(40∶60,V/V) at the flow rate of 1.0 ml/min. The detection wavelength was set at 280 nm,and the column temperature was 30 ℃. The samples size was 10 μl. RESULTS:TLC spectrum showed that the spots of F. arctii concentrated granules and arctiin reference medicinal material had the same color;the linear range of arctiin was 0.5-12.5 μg(r=0.999 8)with the average recovery of 98.41%(RSD=0.81%, n=9). The RSDs of precision,stability,repeatability tests were no more than 1.0%. CONCLUSIONS:The method is feasible and reproducible,and can effectively control the quality of F. arctii concentrated granules.

Optimization of the processing technology of Fructus Arctii by response surface methodology / 中国天然药物

The present study was designed to optimize the processing of Fructus Arctii by response surface methodology (RSM). Based on single factor studies, a three-variable, three-level Box-Behnken design (BBD) was used to monitor the effects of independent variables, including processing temperature and time, on the dependent variables. Response surfaces and contour plots of the contents of total lignans, chlorogenic acid, arctiin, and arctigenin were obtained through ultraviolet and visible (UV-Vis) monitoring and high performance liquid chromatography (HPLC). Fructus Arctii should be processed under heating in a pot at 311 °C, medicine at 119 °C for 123s with flipping frequently. The experimental values under the optimized processing technology were consistent with the predicted values. In conclusion, RSM is an effective method to optimize the processing of traditional Chinese medicine (TCM).

Chemical analysis of raw and processed Fructus arctii by high-performance liquid chromatography/diode array detection-electrospray ionization-mass spectrometry.

BACKGROUND: In traditional Chinese medicine (TCM), raw and processed herbs are used to treat the different diseases. Fructus Arctii, the dried fruits of Arctium lappa l. (Compositae), is widely used in the TCM. Stir-frying is the most common processing method, which might modify the chemical compositions in Fructus Arctii. MATERIALS AND METHODS: To test this hypothesis, we focused on analysis and identification of the main chemical constituents in raw and processed Fructus Arctii (PFA) by high-performance liquid chromatography/diode array detection-electrospray ionization-mass spectrometry. RESULTS: The results indicated that there was less arctiin in stir-fried materials than in raw materials. however, there were higher levels of arctigenin in stir-fried materials than in raw materials. CONCLUSION: We suggest that arctiin reduced significantly following the thermal conversion of arctiin to arctigenin. In conclusion, this finding may shed some light on understanding the differences in the therapeutic values of raw versus PFA in TCM.

Isolation and purification of arctigenin from Fructus Arctii by enzymatic hydrolysis combined with high-speed counter-current chromatography.

Enzymatic hydrolysis pretreatment combined with high-speed counter-current chromatography for the transformation and isolation of arctigenin from Fructus Arctii was successfully developed. In the first step, the extract solution of Fructus Arctii was enzymatic hydrolyzed by ß-glucosidase. The optimal hydrolysis conditions were 40°C, pH 5.0, 24 h of hydrolysis time, and 1.25 mg/mL ß-glucosidase concentration. Under these conditions, the content of arctigenin was transformed from 2.60 to 12.59 mg/g. In the second step, arctigenin in the hydrolysis products was separated and purified by high-speed counter-current chromatography with a two-phase solvent system composed of petroleum ether/ethyl acetate/methanol/water (10:25:15:20, v/v), and the fraction was analyzed by HPLC, ESI-MS, and (1)H NMR spectroscopy. Finally, 102 mg of arctigenin with a purity of 98.9% was obtained in a one-step separation from 200 mg of hydrolyzed sample.

Evaluation of hypoglycemic activity of total lignans from Fructus Arctii in the spontaneously diabetic Goto-Kakizaki rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Arctii, called "Niubangzi" in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity. MATERIALS AND METHODS: Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated. RESULTS: TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats. CONCLUSION: The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.