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Ethnopharmacological relevance Radix Paeoniae Alba ( Baishao , BS), one of the most commonly used traditional Chinese medicinal herbs, has many pharmacological effects including analgesic activity. Previous studies found that sulfur-fumigation, a post-harvest handling process developed to prevent mold contamination of medicinal herbs, altered the quality of BS. However, whether sulfur-fumigation affects the pharmacokinetics, safety and efficacy of BS warrants further investigation. Aim of the study To evaluate the feasibility of sulfur-fumigation as a post-harvest handling process of BS from the viewpoints of pharmacokinetics, safety and efficacy. Materials and methods The pharmacokinetic behaviors of four active components of BS and one characteristic component of sulfur-fumigated BS (S-BS) were evaluated by high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-TQ-MS/MS). The safety was investigated using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) based metabolomics approach after intragastric (i.g.) administration of non-fumigated BS (N-BS) and S-BS in rats. The analgesic efficacy was compared using hot-plate test in mice, after i.g. administration of N-BS and S-BS, at both high and low dosages. Results Systemic exposures of paeoniflorin and oxypaeoniflorin, two analgesic components of BS, were significantly decreased in the S-BS treated group compared to the N-BS treated group, while paeoniflorin sulfonate, one of the sulfur-containing derivatives of S-BS, was detected in all time-points of S-BS treated group with the area under the plasma concentration–time curve (AUC 0−t ) and the maximum plasma concentration (C max ) as high as 7077.06 ± 2232.97 ng/mL*h and 1641.42 ± 634.79 ng/mL respectively, which indicated that sulfur-fumigation altered the pharmacokinetic behaviors of BS. Besides, paeoniflorin sulfonate and its four metabolites with ambiguous toxicities, as well as one endogenous metabolite p-cresol glucuronide, the biomarker of disordered homeostasis of intestinal bacteria and bile acid, were identified as the characteristic metabolites in S-BS administered rats, suggesting that sulfur-fumigation reduced the safety of BS. Furthermore, the analgesic effects at both low and high dosages were decreased in different extent when compared to N-BS administered groups, indicating that sulfur-fumigation weakened the efficacy of BS. Conclusion Sulfur-fumigation altered the pharmacokinetics, as well as reduced the safety and efficacy of BS, suggesting that sulfur-fumigation is not recommended for post-harvest handling of BS. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine practice, crude herbs are often subjected to traditional processing ( Paozhi in Chinese) for a special medicinal purpose. Bran-frying is one of processing methods for Paeoniae Radix Alba (PRA). Previous studies found that paeoniflorin and paeoniflorin sulfonate, a principle bioactive compound and its sulfur-fumigation induced characteristic sulfur-containing derivative, could be used together with sulfur dioxide residue as chemical markers for the quality control of sulfur-fumigated PRA crude material. In this paper, the feasibility of these three markers used for the quality control of bran-fried sulfur-fumigated PRA was further investigated. First, homemade samples of sulfur-fumigated PRA with different sulfur-fumigation duration (0.5–6 h) were bran-fried, and stored for 12 months. Second, the contents of sulfur dioxide residue, paeoniflorin and paeoniflorin sulfonate were dynamically quantified respectively. Third, the variation of the marker contents and their correlation during bran-frying and storage was evaluated. A validation was conducted using commercial bran-fried PRA samples. The results showed that bran-frying caused an averaged reduction of 20% in the content of sulfur dioxide residue, and during the first two months of storage the content of sulfur dioxide residue was decreased by up to 27%, then the content was tending towards stability for the subsequent ten months of storage (RSD = 3.92%). Meanwhile, paeoniflorin and paeoniflorin sulfonate were relatively stable, the contents of which were not affected by bran-frying processing and 12 months of storage. The correlations between the contents of sulfur dioxide residue and paeoniflorin/paeoniflorin sulfonate were obviously influenced by storage duration. Since sulfur dioxide residue is a safety marker, while paeoniflorin and paeoniflorin sulfonate can reflect the inner quality and the impact extent of sulfur-fumigation on the quality of bran-fried PRA respectively, these three chemicals might be used together as markers for the quality control, and consequently to ensure the safety and efficacy of bran-fried PRA. [ABSTRACT FROM AUTHOR]

Exploring processing chemistry, in particular the chemical transformation mechanisms involved, is a key step to elucidate the scientific basis in traditional processing of herbal medicines. Previously, taking Rehmanniae Radix (RR) as a case study, the holistic chemome (secondary metabolome and glycome) difference between raw and processed RR was revealed by integrating hyphenated chromatographic techniques-based targeted glycomics and untargeted metabolomics. Nevertheless, the complex chemical transformation mechanisms underpinning the holistic chemome variation in RR processing remain to be extensively clarified. As a continuous study, here a novel strategy by combining chemomics-based marker compounds mining and mimetic processing is proposed for further exploring the chemical mechanisms involved in herbal processing. First, the differential marker compounds between raw and processed herbs were rapidly discovered by untargeted chemomics-based mining approach through multivariate statistical analysis of the chemome data obtained by integrated metabolomics and glycomics analysis. Second, the marker compounds were mimetically processed under the simulated physicochemical conditions as in the herb processing, and the final reaction products were chemically characterized by targeted chemomics-based mining approach. Third, the main chemical transformation mechanisms involved were clarified by linking up the original marker compounds and their mimetic processing products. Using this strategy, a set of differential marker compounds including saccharides, glycosides and furfurals in raw and processed RR was rapidly found, and the major chemical mechanisms involved in RR processing were elucidated as stepwise transformations of saccharides (polysaccharides, oligosaccharides and monosaccharides) and glycosides (iridoid glycosides and phenethylalcohol glycosides) into furfurals (glycosylated/non-glycosylated hydroxymethylfurfurals) by deglycosylation and/or dehydration. The research deliverables indicated that the proposed strategy could advance the understanding of RR processing chemistry, and therefore may be considered a promising approach for delving into the scientific basis in traditional processing of herbal medicines. [ABSTRACT FROM AUTHOR]

Sulfur fumigation can induce chemical transformation of bioactive components, consequently the alteration of bioactivities or even toxicities of medicinal herbs. Inspecting Chinese patent medicines (CPM) contained sulfur-fumigated constituent herbs is crucial for ensuring the safety and efficacy of CPM. Paeonifiorin sulfonate is a sulfur-fumigation induced compound of Moutan Cortex (MC), one of the main constituent herbs of a commonly used CPM Liu-Wei-Di-Huang-Wan (LWDHW). Herein, we investigated the approach of paeonifiorin sulfonate as a characteristic marker for specifically inspecting LWDHW potentially contained sulfur-fumigated MC (SFMC). First, mimic LWDHW samples contained SFMC (SFMC-LWDHW) and non-fumigated MC (NFMC-LWDHW) were prepared respectively. Second, an LC–MS method was developed and validated to qualitatively and quantitatively determine paeonifiorin sulfonate in the mimic LWDHW samples. Third, the established method was applied to analyze the commercial LWDHW samples. The results showed that paeoniflorin sulfonate could only be detectable in SFMC-LWDHW, but not in NFMC-LWDHW samples. The CPM matrix could enhance the response of paeoniflorin sulfonate in mass spectrometry analysis. In addition, the LOQ, linearity, precision, accuracy and stability were also demonstrated to be acceptable for quantifying paeoniflorin sulfonate in LWDHW. Commercial samples analysis indicated that paeoniflorin sulfonate were detectable in 9 of 10 commercial LWDHW samples, with the content varied between 105.53 μg/g and 438.61 μg/g. All the results suggested that paeoniflorin sulfonate could be used as a characteristic and reliable chemical marker for specifically inspecting commercial LWDHW contained SFMC. This study also provides a new strategy for the quality control of other CPMs potentially produced from sulfur-fumigated constituent herbs. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown. Aim of the study To investigate the chemical profiles and effects of CKF on IBS model. Materials and methods The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated. Results 80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0 g/kg/d. Conclusions CKF could alleviate the symptoms of IBS by modulating the brain–gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF. [ABSTRACT FROM AUTHOR]

Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO 2) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides, changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO 2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO 2 residue in sulfur-fumigated ginseng, it couldn't recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs. • Sulfur-fumigated ginseng affected the chemical profiles of Sijunzi decoction (SJZD). • The evaluations were assessed by metabolomics and glycomics strategies. • Non-saccharide and saccharide components in SJZD were altered by fumigated ginseng. • Ginseng in high-extent fumigation showed more serious effect on SJZD. • Storage reduced SO 2 residue but not recovered changes of fumigated ginseng on SJZD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multi-chromatographic approaches were integrated to compare chemical profiles between MHD and cSHD. • Polysaccharides and small molecules were qualitatively identical between MHD and cSHD. • The contents of albiflorin, paeoniflorin and alkaloids in MHD were lower than those in cSHD. • The content of polysaccharides in MHD was higher than that in cSHD. Chang-Kang-Fang formula (CKF), a multi-herbs traditional Chinese medicine (TCM) prescription for treating irritable bowel syndrome (IBS), has been clinically applied in the traditional form of mixed-herb decoction (MHD), or in the modern form of combined single-herb decoction (cSHD, so called dispensing granule decoction) in the near decades, but the chemical consistency between the MHD and cSHD is still unknown. Herein, a new strategy by integrating multiple-chromatographic approaches to characterize both polysaccharides and small molecules was developed to compare the chemical consistency between MHD and cSHD. Sixteen small molecules were simultaneously qualified and quantified by UPLC-QTOF-MS/MS, the molecular weight distribution of polysaccharides was characterized by HPGPC-ELSD, while the monosaccharide composition and total saccharides content were determined by HPLC-PDA and UV-VIS, respectively. It was found that the molecular weight range and monosaccharide composition of polysaccharides, as well as the composition of small molecules, were identical between MHD and cSHD. However, the contents of berberine, epiberberine, coptisine, palmatine, albiflorin and paeoniflorin in MHD were significantly lower than those in cSHD, whereas the content of polysaccharides in MHD was higher than that in cSHD, indicating that there is a significant difference in the quality between MHD and cSHD, in particular for the relative contents of major small molecules and polysaccharides. Whether or not these quality variations affect the efficacy and safety of CKF deserves further investigation. [ABSTRACT FROM AUTHOR]

• Holistic quality consistency of four origins of Cicadae Periostracum was evaluated by UPLC-TOF-MS/MS. • Thirty-four N -acetyldopamine polymers identified from four origins of Cicadae Periostracum. • The quality of Cryptotympana atrata , Auritibicen flammatus and C. mandrina were consistent with each other, but Platypleura kaempferi not. • The outcomes beneficial for comprehensively utilizing resources and improving standard of Cicadae Periostracum. Cicadae Periostracum, which is derived from the slough of Cicadidae insects, is a commonly used crude drug in traditional Chinese medicine (TCM). As specified in Chinese Pharmacopoeia, Cryptotympana atrata (CA) is the only official species of this crude drug. However, the slough of other three species, i.e., Auritibicen flammatus (AF), Cryptotympana mandrina (CM) and Platypleura kaempferi (PK), have been also used as the origins of Cicadae Periostracum in Chinese herbal market, although whether the quality of these four origins is consistent or not is still unknown. In present study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to qualitatively and quantitatively compare the chemical profiles of the four origins. Totally, 34 N -acetyldopamine polymers were identified from the four origins, including 4 N -acetyldopamine dimers, 11 N -acetyldopamine trimers, 10 N -acetyldopamine tetramers, and 9 N -acetyldopamine pentamers. AF, CM and PK had similar chemical profiles with that of CA. The contents and compositional ratio of the four types of polymers in CA, AF and CM were consistent with each other, but significantly lower or different in PK. All these results suggested that AF and CM might be considered as the potential resources of Cicadae Periostracum concerning their consistent holistic quality, whereas whether PK could be used as potential origin of Cicadae Periostracum or not need further evaluation for their different compositional ratios and contents of the four types of N -acetyldopamine polymers. This is the first study on chemical profiling and comparison of N -acetyldopamine polymers in four origins of Cicadae Periostracum, which is beneficial for potential resources utilization and quality standard improvement of Cicadae Periostracum. [ABSTRACT FROM AUTHOR]