Compatibility with Panax notoginseng (PN) reduced the plasma concentration of triptolide and delayed the Tmax of Tripterygium wilfordii (TW), the sovereign medicine of Qing-Luo Tong-Bi decoction, which hinted the absorption process of triptolide might be involved in decreasing the toxicity in liver and kidney. The absorption of triptolide, triptonide, wilforlide and tripterine from monomer, TW, TW-PN, TW-Caulis Sinomenii (TW-CS) and Qing-Luo Tong-Bi were analyzed in duodenum, jejunum, ileum and colon of rat via single-pass intestinal perfusion model. An UPLC-MS/MS analysis method was developed to determine the concentration of triptolide, triptonide, wilforlide and tripterine in the inlet and outlet. Then Peff, 10 cm%ABS and Ka were calculated based on the perfusate flux, perfusate volume and candidate chemicals concentration. The absorption of triptolide, triptonide, wilforlide and tripterine in duodenum, jejunum, ileum and colon was independent of concentration within range of 3–9 μg/mL. The target compounds, triptolide, triptonide, wilforlide and tripterine from the TW extract, showed higher absorption extent and rate than those administrated alone, and compared with the absorption situation of the chemicals of TW extract, the absorption of triptolide, triptonide and wilforlide of the extract of TW-PN, TW-CS and Qing-Luo Tong-Bi were decreased in these intestinal segments. However, PN-promoted tripterine absorption was observed in the intestine. Modulation of absorption of chemicals in TW by subsidiary herbs may be responsible for reinforcing the actions and neutralizing the adverse effects through compatibility in the formula of Qing-Luo Tong-Bi. PN inhibits the absorption of triptolide of TW and promote the absorption of tripterine.

Huang-Lian Jie-Du decoction (HLJDD), a famous traditional Chinese prescription constituted byRhizoma Coptidis,Radix Scutellariae,Cortex PhellodendriandFructus Gradeniae, has notable characteristics of dissipating heat and detoxification, interfering with tumors, hepatic diseases, metabolic disorders, inflammatory or allergic processes, cerebral diseases and microbial infections. Based on the wide clinical applications, accumulating investigations about HLJDD focused on several aspects: (1) chemical analysis to explore the underlying substrates responsible for the therapeutic effects; (2) further determination of pharmacological actions and the possible mechanisms of the whole prescription and of those representative ingredients to provide scientific evidence for traditional clinical applications and to demonstrate the intriguing molecular targets for specific pathological processes; (3) pharmacokinetic feature studies of single or all components of HLJDD to reveal the chemical basis and synergistic actions contributing to the pharmacological and clinically therapeutic effects. In this review, we summarized the main achievements of phytochemical, pharmacological and pharmacokinetic profiles of HLJDD and its herbal or pharmacologically active chemicals, as well as our understanding which further reveals the significance of HLJDD clinically.

Polysaccharides in carob fruit, including carob bean gum (also known as carob gum, locust bean gum) and carob fiber, are widely used in industries such as food, pharmaceuticals, paper, textile, oil well drilling and cosmetics. Carob bean gum is a galactomannan obtained from the seed endosperm of carob tree and the fiber is obtained by removing most of soluble carbohydrates in carob pulp by water extraction. Both the gum and fiber are beneficial to health for many diseases such as diabetes, bowel movements, heart disease and colon cancer. This article reviewed the composition, properties, food applications and health benefits of polysaccharides from carob fruit.

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.

Background: Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer’s disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose: To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods: The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of β-amyloid (Aβ)_{25– 35}-induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and Aβ as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, real-time quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in Aβ_25-35-stimulated BV2 microglia. Results: Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and Aβ_25-35-stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in Aβ_25-35-stimulated BV2 cells. In AD mice, more microglia were clustered in the Aβ-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in Aβ_25-35-stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion: HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD. Graphical Abstract: