Establishing an integrated, four-dimensional quality assessment system for traditional Chinese medicine: A case study of Shuanghuanglian oral liquid.

The quality of traditional Chinese medicine (TCM) is the premise to ensure its safety and effectiveness in clinical application. In this study, a complete quality control system for four-dimensional fingerprinting of TCM was innovatively constructed based on multiple detection techniques, and the quality of Shuanghuanglian oral liquid (SHL) was evaluated. Electrochemical fingerprinting (ECFP) as an emerging method without pretreatment provides rich and quantifiable information for SHL samples. The first quantitative ECFP of SHL was developed by the B-Z oscillation system. Eight characteristic parameters were analyzed and a good linear relationship was found between the oscillation lifetime and sample volume, by which the calculated values of the added sample volume (VL) showed different fluctuations between samples. What is more, high-performance liquid chromatography five-wavelength fusion fingerprint (HPLC-FWFP), GC fingerprint (GC-FP), and UV quantum fingerprint (UV-QFP) was established. Meanwhile, the purity of the peaks of the HPLC-FWFP was verified by the dual-wavelength absorption coefficient ratio spectrum (DWAR). Equal weighted ratio quantitative fingerprinting method (EWRQFM) was successfully proposed to extract all potential features for the overall quality assessment of the samples. Finally, a comprehensive evaluation strategy was proposed, namely the variation coefficient weighting algorithm (VCWA). The results of qualitative and quantitative evaluation of HPLC-FWFP, GC-FP, electrochemical quantum fingerprints (EC-QFP), and UV-QFP were integrated by this method. The established evaluation system is also a suitable strategy to control the quality of other TCM preparations.

Evaluating the quality consistency of antiviral oral liquid by high-performance liquid chromatography five-wavelength matched average fusion fingerprint combined with electrochemical fingerprint and ultraviolet spectral quantum fingerprint.

The antiviral oral liquid (AOL) was an antiviral drug currently in clinical trials against coronavirus disease 2019. This study aimed to improve its quality consistency evaluation method using fingerprint techniques from several aspects. First, the five-wavelength matched average fusion fingerprint (FMAFFP) for HPLC, electrochemical fingerprint (ECFP), and ultraviolet spectral quantum fingerprint (UVFP) was established for 22 samples, respectively. Their quality was then assessed using the average linear quantitative fingerprint method, and 22 samples were classified into eight quality grades. OPLS and PCA were then used further to explore the characteristic parameters of these three fingerprints. Five compounds were quantified simultaneously for the first time, and then the relationship between the average linear quantitative similarity (PL) and the sum of the five quantitative components (P5c) was investigated. A linear correlation (r ≥ 0.9735) between PL and P5c suggested that PL may be used to predict chemical content. Finally, to investigate the antioxidant potential of the AOL, correlation analyses were performed for FMAFFP peaks-PEC and UVFP peaks-PEC, respectively, where the PEC value was defined as the quantitative similarity of ECFP. The Pearson correlation coefficient and gray correlation analysis were consistent, allowing us to initially explore the antioxidant capacity of the unidentified components of the samples. This study researched AOL using multidimensional fingerprints to provide a comprehensive and reliable method for quality consistency control of herbal compound preparations.

Anti-inflammation activity of Zhizi Jinhua Pills and overall quality consistency evaluation based on integrated HPLC, DSC and electrochemistry fingerprints.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhizi Jinhua Pills (ZZJHP), a compound preparation composed of 8 traditional Chinese medicines (TCM), is widely used clinically to clearing heat, purging fire, cooling blood and detoxifying. However, the studies on its pharmacological activity and the determination of active compounds are relatively few. There is a lack of quality control methods that can reflect the effectiveness of the drug. AIM OF THE STUDY: The objective was to construct fingerprint profiles, conduct a spectrum-effect relationship study and establish an overall quality control method for ZZJHP through anti-inflammatory and redox activity studies. MATERIALS AND METHODS: Firstly, anti-inflammatory activity was tested using the xylene-induced ear edema model in mice. Then, Five-wavelength fusion HPLC fingerprint, electrochemical fingerprint, and Differential scanning calorimetry (DSC) profiling were established to evaluate ZZJHP more comprehensively, where Euclidean quantified fingerprint method (EQFM) was proposed for the similarity assessment of these three fingerprints. Moreover, the spectrum-activity relationship of HPLC-FP and DSC-FP with electrochemical activity helped explore the active components or ranges in the fingerprint. Finally, integrated analysis of HPLC, DSC and electrochemistry were used for the quality screen of samples from different manufacturers. RESULTS: ZZJHP was found to significantly decrease the levels of both TNF-α and IL-6 in the mice. Qualitatively, the integrated similarity Sm of 21 samples were all greater than 0.9, indicating the great consistency in chemical composition. Quantitatively, 9 batches of samples were classified as Grade1∼4; 6 batches of samples were classified as Grade5∼7 due to higher PINT; 6 batches of samples were classified as Grade4∼5 due to lower PINT. EQFM can qualitatively and quantitatively characterize the fingerprint profile information from an overall perspective. CONCLUSIONS: This strategy will contribute to the quantitative characterization of TCM and promote the application of fingerprint technology in the phytopharmacy field.

A Study on the Mechanism of the Sedative-hypnotic Effect of Cinnamomum camphora chvar. Borneol Essential Oil Based on Network Pharmacology.

In this paper, we investigated the sedative-hypnotic effect of Cinnamomum camphora chvar. Borneol essential oil (BEO, 16.4% borneol), a by-product of steam distillation of Cinnamomum camphora chvar. Borneol, from which natural crystalline borneol (NCB, 98.4% borneol) is obtained. Using locomotor activity tests and pentobarbital sodium-induced sleep test, it was found that BEO significantly reduced locomotor activity (p < 0.05), shortened sleep latency (p < 0.0001), prolonged sleep duration (p < 0.05), and had a sedative-hypnotic effect. We constructed the "components-targets-signaling pathways" and "proteinprotein interaction" (PPI) network of BEO using network pharmacology. The results show that the 24 active components of BEO acted on 17 targets, mainly through response to alkaloid and catecholamine transport, and neuroactive ligand-receptor interaction. The PPI network identified 12 key proteins, mainly dopamine receptor (DR)D2, opioid receptor mu 1 (OPRM1), and opioid receptor kappa 1 (OPRK1), and we further analyzed the active components and targets of BEO through molecular docking. The results showed that the active components and targets obtained by network pharmacology analyses had good binding activity, which reflected their multi-component, multi-target, multi-pathway action characteristics. This paper provides a theoretical basis for further study of the mechanism of action of BEO in the treatment of insomnia.

[Connotation of Baimai disease and analysis of compatibility and usage of Baimai Ointment: based on Tibetan medicine theory].

Baimai is a complex of structure and function with the characteristics of wide distribution, complex structure, and multi-dimensional functions. Baimai, consisting of the channels in brain, the internal hidden channels connecting the viscera, and the external channels linking the limbs, governs the sensory, motor, and information transmission functions of human. According to Tibetan medicine, Baimai functions via "Long"(Qi) which moves in Baimai. "Long" is rough, light, cold, tiny, hard, and dynamic. The dysfunction of Baimai is manifested as numbness, swelling and pain, stiffness, atrophy, contracture, disability, hyperactivity, etc. The clinical manifestations of Baimai disease are facial paralysis, limb numbness, hemiplegia, contracture and rigidity, pain, opistho-tonos, paralysis, unconsciousness, head tremor, aphasia and tongue stiffness, and other abnormalities in facial consciousness, limb movement, and tactile sensation. Baimai Ointment for external use is used for the treatment of Baimai disease. It is mainly composed of medicinals which are spicy and bitter, warm, soft, mild, heavy, moist, and stable, and thus it is effective for the rough, light, cold, tiny, hard, and dynamic "Long" of Baimai disease. In clinical practice, it is mainly used for musculoskeletal diseases, such as osteoarthritis, scapulohumeral periarthritis, cervical spondylosis, low back pain, myofascitis, and tenosynovitis, nervous system diseases, such as paralysis and shoulder-hand syndrome, and limb stiffness caused by stroke, spastic cerebral palsy, trigeminal neuralgia, and facial neuritis, and limb motor and sensory dysfunction caused by trauma. According to the main symptoms of Baimai disease such as stiffness, rigidity, contraction, numbness, sensory disturbance and pain, clinicians should apply the Baimai Ointment via the inunction treatment of Tibetan medicine and in combination with Huo'ermai therapy and physiotherapy.

The anti-inflammatory potential of Cinnamomum camphora (L.) J.Presl essential oil in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol was widely used in traditional Chinese medicine formulas due to its pharmacological activities, e.g. sedative, anti-inflammatory, and anti-ischemic properties. Cinnamomum camphora (L.) J.Presl essential oil (BEO) is a by-product of natural crystalline borneol (NCB) production obtained by steam distillation of Cinnamomum camphora (L.) J.Presl leaves, and borneol was the main component of BEO. This study aims to investigate the anti-inflammatory effect of BEO and its corresponding mechanisms through in vitro and in vivo studies. MATERIALS AND METHODS: Human erythrocyte membrane stability assay and the acute inflammation murine model (xylene-induced ear edema) were chosen to evaluate the anti-inflammatory effect of BEO. Expression of inflammatory mediators, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α) was determined by real-time quantitative polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISA). The functional compounds in the BEO were identified by using gas chromatography-mass spectrometry (GC-MS). The steady-state transdermal diffusion rates of BEO and BEO nano-emulsion with were also determined in this study. Cytotoxicity of BEO was analyzed by cell counting kit-8 (CCK-8) assay. RESULTS: The BEO showed a high human erythrocyte membrane stabilization by inhibiting heat-induced hemolysis (IC50 = 5.29 mg/mL) and hypotonic solution-induced hemolysis (IC50 = 0.26 mg/mL) in vitro. The BEO was topically applied to mice auricles, both single and repeated administration significantly reduced xylene-induced auricle swelling (p < 0.0001). Expression of inflammatory mediators, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α) in serum and tissue was significantly downregulated (p < 0.05), so as to the mRNA expression of IL-1ß (p＜0.05) and TNF-α (p < 0.001). A total of 43 components were identified and quantified by GC-MS. The most abundant was borneol [178.3 mg/mL, 20.9% (m/v)], followed by ß-caryophyllene (116.3 mg/mL), camphor (115.2 mg/mL), and limonene (89.4 mg/mL). For determining the skin permeability of BEO, the steady-state transdermal diffusion rates of BEO and BEO nano-emulsion were determined to be 6.7 and 8.9 mg/cm2·h, respectively. CONCLUSION: It is suspected that the anti-inflammatory effects in vivo and in vitro were derived from the above-mentioned components in the BEO. These findings will facilitate the development of BEO as a new and natural therapeutic agent for inflammatory skin conditions.

Cytotoxic Withanolides from the Whole Herb of Physalis angulata L.

Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. Two new withanolides (1-2), together with six known analogues (3-8), were isolated from the whole plant of Physalis angulata L. The structures of these new compounds were determined on the basis of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The withanolides exhibited strong cytotoxic activities against A549, Hela and p388 cell lines. Furthermore, compounds 1 and 2 induced typical apoptotic cell death in A549 cell line according to the evaluation of the apoptosis-inducing activity by flow cytometric analysis.