The Potential Application of Aloe Barbadensis Mill. as Chinese Medicine for Constipation: Mini-Review.

Aloe barbadensis Mill. has a long history of medicinal use in the annals of traditional Chinese medicine, wherein it has garnered considerable renown. Its multifaceted therapeutic properties, characterized by its anti-inflammatory and antibacterial attributes, alongside its established efficacy as a laxative agent, have been extensively documented. This review commences with an exploration of the nomenclature, fundamental characteristics, and principal constituents of Aloe barbadensis Mill. responsible for its laxative effects. Subsequently, we delve into an extensive examination of the molecular mechanisms underlying Aloe barbadensis Mill.'s laxative properties, types of constipation treatments, commercially available preparations, considerations pertaining to toxicity, and its clinical applications. This review aims to serve as a comprehensive reference point for healthcare professionals and researchers, fostering an enhanced understanding of the optimal utilization of Aloe barbadensis Mill. in the treatment of constipation.

Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing Injection in the treatment of coronavirus disease 2019.

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.

Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of gut-liver axis.

BACKGROUND: Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses. Nevertheless, the underlying molecular mechanisms largely remained elusive. AIM: To determine the hepatoprotective effects of SHE on ethanol-triggered liver damage and further elucidate its potential mechanisms. METHODS: In the present study, the Sprague-Dawley rats were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without SHE (300 and 600 mg/kg/d bw) for 8 weeks. The levels of serum biomarkers (ALT, AST and LDH) and LPS were detected by biochemical assay kits and endotoxin detection LAL kit, respectively. The histopathological changes of liver and intestinal tissues were observed by hematoxylin and eosin (H&E) staining and Transmission electron microscope (TEM). The expressions of CD14, TLR4, MyD88, NF-κB, Iκ-B, P-Iκ-B and TNF-α in liver, and ZO-1 and occludin in intestine were determined by western blot. The faecal microbial composition was determined by16S rRNA Gene Sequencing Analysis. RESULTS: Biochemical and histopathological analysis revealed that SHE significantly alleviated the lipid deposition and inflammation response in liver induced by ethanol. SHE remarkably inhibited the TLR4 pathway and its downstream inflammatory mediators, and up-regulated the expressions of ZO-1 and occludin in the intestine. The further investigations suggested SHE dramatically reversed ethanol-induced alterations in the intestinal microbial flora and decreased the generation of gut-derived endotoxin. CONCLUSION: In summary, SHE probably modulated abnormalities of gut-liver axis and inhibited TLR4-associated inflammatory mediators activation to exert its hepatoprotective properties. These findings suggested that SHE as a traditional therapeutic options which may play an essential role in protecting against the chronic ethanol-triggered liver injury.

Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines.

Inhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons. When co-applied with the classical benzodiazepine diazepam, curcumol further potentiated GABA-induced currents. In contrast, in the presence of a saturating concentration of menthol, a positive modulator for GABAAR, curcumol failed to further enhance GABA-induced currents, suggesting shared mechanisms underlying these two agents on GABAARs. Moreover, the benzodiazepine antagonist flumazenil did not alter the enhancement of GABA response by curcumol and menthol, but abolished that by DZP. Finally, mutations at the ß2 or γ2 subunit predominantly eliminated modulation of recombinant GABAARs by curcumol and menthol, or diazepam, respectively. Curcumol may therefore exert its actions on GABAARs at sites distinct from benzodiazepine sites. These findings shed light on the future development of new therapeutics drugs targeting GABAARs.

[Progress of regulation of leukemia stem cells of chronic myeloid leukemia by autophagy].

Leukemia stem cells (LSC) that were found in chronic myeloid leukemia (CML) responsible for the abnormal proliferation with the potential of self-renewal and multi-directional differentiation are involved in the pathophysiological process for drug resistance and relapse of CML. Autophagy, a conservative lysosomal degradation process that mediates cell degradation and recycling process, plays crucial roles in maintaining the homeostasis and function of intracellular environment. Recent studies suggested that autophagy is involved in the regulation of LSC differentiation and also closely related to the chemo-sensitivity of CML. In this review, we focused on the role of autophagy on chemotherapy sensitivity of CML as well as the leukemia stem cell function for the development of new anti-leukemia drugs.

Flavonoids from Radix Tetrastigmae improve LPS-induced acute lung injury via the TLR4/MD-2-mediated pathway.

Total flavonoids isolated from Radix Tetrastigmae (RTFs) possess immunomodulatory activity, particularly on inflammation. In mice with lipopolysaccharide (LPS)­induced acute lung injury (ALI), treatment with RTFs at 40, 80 and 160 mg/kg significantly reduced leukocyte infiltration, improved histopathological changes in lung tissues and decreased the LPS­induced production of several inflammatory mediators in the bronchoalveolar lavage fluid (BALF), which included the chemotatic factors, granulocyte colony­stimulating factor, monocyte inflammatory protein­1α and B­lymphocyte colony inflammatory cytokines, including interleukin (IL)­1ß, IL­6, IL­12p40 and tumor necrosis factor­α, in a dose­dependent manner. In addition, the expression of the Toll­like receptor 4 (TLR4)/myeloid differentiation factor­2 (MD­2) compound, the phosphorylation of p38 mitogen­activated protein kinase (p38MAPK), c­Jun N­terminal kinase (JNK) and nuclear transcription factor­κB (NF­κB), in addition to the DNA binding activity of NF­κB p65 in lung tissues, were all attenuated following RTF treatment. However, RTF treatment had no effect on extracellular signal­regulated kinase (ERK). In conclusion, RTFs contributed to the regulation of LPS­induced ALI through the TLR4/MD-2-mediated NF­κB, JNK and p38MAPK pathways. This may be a potential therapeutic option for the treatment of inflammatory diseases.

L-Tetrahydropalmatine alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice.

Chronic pain is categorized as inflammatory and neuropathic, and there are common mechanisms underlying the generation of each pain state. Such pain is difficult to treat and the treatment at present is inadequate. Corydalis yanhusuo is a traditional Chinese medicine with demonstrated analgesic efficacy in humans. The potential antihyperalgesic effect of its active component is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatment of headache and other mild pain. However, little is known about its analgesic effect on chronic pain and its mechanism. Here, we report that L-THP exerts remarkable antihyperalgesic effects on neuropathic and inflammatory pain in animal models. Neuropathic hypersensitivity was induced by segmental spinal nerve ligation and inflammatory hypersensitivity was induced by an intraplantar injection of complete Freund's adjuvant. To determine the receptor mechanism underlying the antihyperalgesic actions of L-THP, we used SCH23390, an antagonist of a dopamine D1 receptor, in an attempt to block the antihyperalgesic effects of L-THP. We found that L-THP (1-4 mg/kg, i.p.) produced a dose-dependent antihyperalgesic effect in spinal nerve ligation and complete Freund's adjuvant models. The antihyperalgesic effects of L-THP were abolished by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg). Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findings suggest that L-THP may ameliorate mechanical hyperalgesia by enhancing dopamine D1 receptor-mediated dopaminergic transmission.

(+)-Borneol attenuates oxaliplatin-induced neuropathic hyperalgesia in mice.

Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is difficult to treat and responds poorly to common analgesics, which represents a clinical challenge. (+)-Borneol, a bicyclic monoterpene present in the essential oil of plants, is used for analgesia and anesthesia in traditional Chinese medicine. Although borneol has an antinociceptive effect on acute pain models, little is known about its effect on chemotherapy-induced neuropathic pain and its mechanism. We found that (+)-borneol exerted remarkable antihyperalgesic effects in a mouse model of oxaliplatin-induced neuropathic pain. In addition, (+)-borneol blocked the action of the transient receptor potential ankyrin 1 agonist in mechanical and cold stimulus tests. Repeated treatment with (+)-borneol did not lead to the development of antinociceptive tolerance and did not affect body weight and locomotor activity. (+)-Borneol showed robust analgesic efficacy in mice with neuropathic pain by blocking transient receptor potential ankyrin 1 in the spinal cord and may be a useful analgesic in the management of neuropathic pain.

[Analysis of different forms Linderae Radix based on HPLC and NIRS fingerprints].

Three different forms of Linderae Radix were evaluated by HPLC combined with NIRS fingerprint. The Linderae Radix was divided into three forms, including spindle root, straight root and old root. The HPLC fingerprints were developed, and then cluster analysis was performed using the SPSS software. The near-infrared spectra of Linderae Radix was collected, and then established the discriminant analysis model. The similarity values of the spindle root and straight root all were above 0.990, while the similarity value of the old root was less than 0.850. Two forms of Linderae Radix were obviously divided into three parts by the NIRS model and Cluster analysis. The results of HPLC and FT-NIR analysis showed the quality of Linderae Radix old root was different from the spindle root and straight root. The combined use of the two methods could identify different forms of Linderae Radix quickly and accurately.

[Determination of main active components in crude and processed Corydalis Rhizoma samples from different habitats].

OBJECTIVE: To compare the content of water, ethanol soluble extracts and tetrahydropalmatine in crude and processed Corydalis Rhizoma samples from different habitats. METHODS: Corydalis Rhizoma was processed according to the optimum processing of the Chinese Pharmacopoeia (2010 edition), and then, the difference of the content of water,ethanol soluble extracts and tetrahydropalmatine in crude and processed Corydalis Rhizoma samples were analyzed and compared. RESULTS: From 14 different batches of Corydalis Rhizoma studies, the content of water, ethanol soluble extracts and tetrahydropalmatine in crude Corydalis Rhizoma was 12.8%-14.8%, 16.5%-19.6% and 0.043%-0.075%, respectively; As for Corydalis Rhizoma after processing with vinegar,the content of water, ethanol soluble extracts and tetrahydropalmatine was 7.58%-11.7%, 17.8%-23.5% and 0.046%-0.079%, respectively. CONCLUSION: The content of water, ethanol soluble extracts and tetrahydropalmatine varies slightly in the same type of samples from different habitats,which might be due to the difference in soil and climate in each habitat.

[Comparison of the distribution of breviscapine in the brain by different administration routes].

By comparing the drug distribution of breviscapine administered intranasally, orally and intrgvenous injected in rats' brain. After 0.4 mg x kg(-1) breviscapine was given by tail vein, intranasal and gastric perfusion administration to SD rats, cerebrospinal fluid was obtained by erebellomedllery cisternal puncture at different times. 125I labeling was used to determine the drug content of cerebrospinal fluid, cerebrum, cerebellum, medulla oblongata, olfactory region, olfactory bulb and blood in rats. AUCs were calculated by trapezoidal rule. The results showed that AUCs(0-240 min) (microg x min x g(-1)) of brain tissues were 11.686 +/- 1.919, 5.676 +/- 1.025, 7.989 +/- 0.925, 7.956 +/- 1.159, 17.465 +/- 2.136, 24.2 +/- 2.906 and 78.51 +/- 12.05, respectively, in the intranasal administration group; while those in the tail vein administration groups were 6.79 +/- 0.661, 6.251 +/- 0.40, 10.805 +/- 1.161, 9.146 +/- 1.04, 9.892 +/- 1.532, 7.871 +/- 0.842 and 173.91 +/- 10.02; and oral administration group were 0.868 +/- 0.167, 1.708 +/- 0.266, 2.867 +/- 0.725, 2.067 +/- 0.313, 1.361 +/- 0.308, 1.206 +/- 0.255 and 45.2 +/- 7.52, respectively. AUCs(0-240 min) of the brain tissues after oral, tail vein and intranasal administration were 22.29%, 29.18%, 95.49% of that of blood, respectively, it means that the absorption rate and drug distribution in the brain tissues after intranasal administration were higher than those of oral and tail vein administration. It is worth to investigate further the pharmacodynamic relationship.

[Novel method for the evaluation of the synchronicity of the chemomic release/dissolution of multi-component traditional Chinese medicines].

Due to the diversity of components within the traditional Chinese medicines (TCMs), the release profiles of the components in the TCM dosage forms vary dramatically and no quantification method is available to determine the variance yet. Based upon the principles of Kalman filter method, the authors defined a new parameter, relative chemomic error (epsilon), to evaluate the asynchronous nature of the components in TCMs, and a derivative parameter as synchronization factor (SF) to quantify the synchronicity of the chemome of the TCMs. The average synchronization factor (SF(av)) was accordingly derived to simultaneously quantify the release/dissolution profiles of the multi-components in TCMs. Randomly generated simulation data were processed to demonstrate the chemomic data processing and the methodology. The results indicated that the novel parameter epsilon was well correlated (r = 0.996 8) with the coefficient of variation from the conventional release profiles of all the components. As the asynchronicity was the intrinsic characteristics of the multi-component TCMs, the synchronicity might be a new target of quality control of TCMs. The methods established by this report can be used a quantitative tool for the evaluation of the chemomic release synchronization of TCMs.

[Application of the theories of materiomic release kinetics to the evaluation of the sustained release kinetics and synchronicity of yinqiaojiedu honeyed pills].

Yinqiaojiedu honeyed pills were equally divided into 1/4, 1/8, 1/12, and 1/16 parts. The materiomics release rates within 12 h of the intact Yinqiaojiedu honeyed pills and the divided granules were determined by the paddle method with a rotate speed at 100 r x min(-1), and the materiome was quantified by UV-scan and Kalman filter methods. The intact Yinqiaojiedu honeyed pills behaved typical sustained release profiles, while the well-divided portions also maintained a sustained release profile over 2-4 h. The release rates were well correlated with the extents for the divisions of the pills. The Weibull distribution parameters, Td and T50, were reduced in line with the particle size, indicating that the ways of administration of the pills may play a role in the in vivo pharmacokinetics of the pills. The visualization results showed obvious difference of materiomic release synchronicities between the intact pills and the equally divided particles, and the divisions enhanced the asynchronization. Therefore the novel theory of materiomic release/dissolution kinetics of traditional Chinese medicines (TCMs) quantitatively proved the traditional dosage form, namely, honeyed pills, as a prototype of the sustained-release dosage form with a visualization of the scientific connotation to the old saying in the classics of TCM, Pills, the moderate ones in action. In terms of materiome increase for each period of the release profiles, the materiomic release synchronicity was visually demonstrated. The novel theories provided methodological basis for the evaluation of traditional dosage forms and the design of the modern drug delivery systems for TCMs.

[Effects of volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root on proinflammatory cytokine expression and regulation].

OBJECTIVE: To study the effects of volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root (OSS) on proinflammatory cytokine expression and regulation in rats. METHOD: OA and LPS were injected intravenously to rats to develop acute lung injury (ALI). The rats were treated with OSS (45.19 microL kg(-1)). The pathological sections of lung tissue were prepared and observed in acute lung injury rats. The expression of nuclear factor-kappa B p65 (NF-kappaB p65), intercellar adhesion molecule CD54, and NF-kappaB p65 mRNA were determined in lung cells. RESULT: volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root significantly inhibited the expression of CD54, the activation of NF-kappaB p65, and the transcription of NF-kappaB p65 mRNA. CONCLUSION: OSS can reduce the expression of CD54 and NF-kappaB p65 protein synthesis, which may be its anti-inflammatory molecular mechanisms.