In-vitro antioxidant and anti-inflammatory potential along with p.o. pharmacokinetic profile of key bioactive phytocompounds of Snow Mountain Garlic: a comparative analysis vis-à-vis normal garlic.

Snow mountain garlic (SMG) is a trans-Himalayan medicinal plant used in the traditional medicine system for several ailments, including inflammatory arthritis. Research studies are insufficient to validate its folk medicinal applications. In the present study, the comparative abundance of its key bioactive phytocompounds, viz., S-allyl-L-cysteine (SAC), alliin, and S-methyl-L-cysteine (SMC) against normal garlic were assessed using the LC-MS/MS-MRM method. In addition, the study also explored the antioxidant and anti-inflammatory potency of crude extract of SMG and purified signature phytocompounds (i.e., SMC, SAC, and alliin) in comparison with normal garlic and dexamethasone in LPS-stimulated RAW264.7 macrophage cells. The LC-MS/MS-MRM study revealed significant differences among SMG and normal garlic, viz., alliin 22.8-fold higher in SMG, and SMC could be detected only in SMG. In the bioassays, SMG extract and purified signature phytocompounds significantly downregulated oxidative damage in activated macrophages, boosting endogenous antioxidants' activity. SMG extract-treated macrophages significantly suppressed NF-κB expression and related inflammatory indicators such as cytokines, COX-2, iNOS, and NO. Notably, the observed anti-inflammatory and antioxidant bioactivities of SMG extract were comparable to signature phytocompounds and dexamethasone. In addition, SAC being uniformly found in SMG and normal garlic, its comparative pharmacokinetics was studied to validate the pharmacodynamic superiority of SMG over normal garlic. Significantly higher plasma concentrations (Cmax), half-life (t1/2), and area under curve (AUC) of SAC following SMG extract administration than normal garlic validated the proposed hypothesis. Thus, the abundance of bioactive phytocompounds and their better pharmacokinetics in SMG extract might be underlying its medicinal merits over normal garlic.

Anti-inflammatory effect and pharmacokinetics of dehydroandrographolide, an active component of Andrographis paniculata, on Poly(I:C)-induced acute lung injury.

Acute lung injury (ALI) is a common and critical respiratory disorder caused by various factors, with viral infection being the leading contributor. Dehydroandrographolide (DAP), a constituent of the Chinese herbal plant Andrographis paniculata, exhibits a range of activities including anti-inflammatory, in vitro antiviral and immune-enhancing effects. This study evaluated the anti-inflammatory effects and pharmacokinetics (PK) profile of DAP in ALI mice induced by intratracheal instillation of Poly(I:C) (PIC). The results showed that oral administration of DAP (10-40 mg/kg) effectively suppressed the increase in lung wet-dry weight ratio, total cells, total protein content, accumulation of immune cells, inflammatory cytokines and neutrophil elastase levels in bronchoalveolar lavage fluid of PIC-treated mice. DAP concentrations, determined by an LC-MS/MS method, in plasma after receiving DAP (20 mg/kg) were unchanged compared to those in normal mice. However, DAP concentrations and relative PK parameters in the lungs were significantly altered in PIC-treated mice, exhibiting a relatively higher maximum concentration, larger AUC, and longer elimination half-life than those in the lungs of normal mice. These results demonstrated that DAP could improve lung edema and inflammation in ALI mice, and suggested that lung injury might influence the PK properties of DAP, leading to increased lung distribution and residence. Our study provides evidence that DAP displays significant anti-inflammatory activity against viral lung injury and is more likely to distribute to damaged lung tissue.

Optimization for ultrasonic-microwave synergetic extraction of total iridoid glycosides and screening of analgesic and anti-inflammatory active fractions from patrinia scabra Bunge (Valerianaceae).

BACKGROUND: Patrinia scabra Bunge is a well-known herbal medicine for its favorable treatment on inflammatory diseases owing to its effective ingredients, in which iridoid glycoside plays an extremely significant role. This article aimed to improve the content of total iridoid glycosides in crude extract through a series optimization of extraction procedure. Moreover, considering that both pain and inflammation are two correlated responses triggered in response to injury, irritants or pathogen, the article investigated the anti-inflammatory and analgesic activities of P. scabra to screen out the active fraction. METHOD: P. scabra was extracted by ultrasonic-microwave synergistic extraction (UMSE) to obtain total iridoid glycosides (PSI), during which a series of conditions were investigated based on single-factor experiments. The extraction process was further optimized by a reliable statistical method of response surface methodology (RSM). The elution fractions of P. scabra extract were prepared by macroporous resin column chromatography. Through the various animal experiment including acetic acid-induced writhing test, formalin induced licking and flinching, carrageenan-induced mice paw oedema test and xylene-induced ear edema in mice, the active fractions with favorable analgesic and anti-inflammatory effect were reasonably screen out. RESULTS: The content of PSI could reach up to 81.42 ± 0.31 mg/g under the optimum conditions as follows: ethanol concentration of 52%, material-to-liquid ratio of 1:18 g/mL, microwave power at 610 W and extraction time of 45 min. After gradient elution by the macroporous resin, the content of PSI increased significantly. Compared with other concentrations of elution liquid, the content of PSI in 30 and 50% ethanol eluate was increased to reach 497.65 and 506.90 mg/g, respectively. Owing to the pharmacology experiment, it was reasonably revealed that 30 and 50% ethanol elution fractions of P. scabra could relieve pain centrally and peripherally, exhibiting good analgesic and anti-inflammatory activities. CONCLUSION: Patrinia scabra possessed rich iridoids and exhibited significant analgesic and anti-inflammatory activities.

Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis.

BACKGROUND: Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). RESULTS: We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. CONCLUSION: This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

Health Benefits and Pharmacological Properties of Carvone.

Carvone is a monoterpene ketone contained in the essential oils of several aromatic and medicinal plants of the Lamiaceae and Asteraceae families. From aromatic plants, this monoterpene is secreted at different concentrations depending on the species, the parts used, and the extraction methods. Currently, pharmacological investigations showed that carvone exhibits multiple pharmacological properties such as antibacterial, antifungal, antiparasitic, antineuraminidase, antioxidant, anti-inflammatory, and anticancer activities. These studies were carried out in vitro and in vivo and involved a great deal of knowledge on the mechanisms of action. Indeed, the antimicrobial effects are related to the action of carvone on the cell membrane and to ultrastructural changes, while the anti-inflammatory, antidiabetic, and anticancer effects involve the action on cellular and molecular targets such as inducing of apoptosis, autophagy, and senescence. With its multiple mechanisms, carvone can be considered as natural compounds to develop therapeutic drugs. However, other investigations regarding its precise mechanisms of action as well as its acute and chronic toxicities are needed to validate its applications. Therefore, this review discusses the principal studies investigating the pharmacological properties of carvone, and the mechanism of action underlying some of these properties. Moreover, further investigations of major pharmacodynamic and pharmacokinetic studies were also suggested.

Orally Deliverable Dual-Targeted Pellets for the Synergistic Treatment of Ulcerative Colitis.

PURPOSE: The effective treatment of ulcerative colitis (UC) poses substantial challenges, and the aetiopathogenesis of UC is closely related to infectious, immunological and environmental factors. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract. METHODS: Berberine (BBR) and Atractylodes macrocephala Koidz (AM) volatile oil, derived from the Chinese herbs Coptis chinensis Franch and Atractylodes macrocephala Koidz, have anti-inflammatory and immunomodulatory activities. In this study, we prepared colon-targeted pellets loaded with BBR and stomach-targeted pellets loaded with AM volatile oil for the synergistic treatment of UC. The Box-Behnken design and ß-cyclodextrin inclusion technique were used to optimize the enteric coating formula and prepare volatile oil inclusion compounds. RESULTS: The two types of pellets were spherical and had satisfactory physical properties. The pharmacokinetic results showed that the AUC and MRT values of the dual-targeted (DPs) pellets were higher than those of the control pellets. In addition, in vivo animal imaging confirmed that the DPs could effectively deliver BBR to the colon. Moreover, compared with sulfasalazine and monotherapy, DPs exerted a more significant anti-inflammatory effect by inhibiting the expression of inflammatory factors including IL-1ß, IL-4, IL-6, TNF-α and MPO both in serum and tissues and enhancing immunity by decreasing the production of IgA and IgG. CONCLUSION: The DPs play a synergistic anti-UC effect by exerting systemic and local anti-inflammatory and provide an effective oral targeted preparation for the treatment of UC.

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems.

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety.

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb-drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications.

Euphausia superba, commonly known as krill, is a small marine crustacean from the Antarctic Ocean that plays an important role in the marine ecosystem, serving as feed for most fish. It is a known source of highly bioavailable omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In preclinical studies, krill oil showed metabolic, anti-inflammatory, neuroprotective and chemo preventive effects, while in clinical trials it showed significant metabolic, vascular and ergogenic actions. Solvent extraction is the most conventional method to obtain krill oil. However, different solvents must be used to extract all lipids from krill because of the diversity of the polarities of the lipid compounds in the biomass. This review aims to provide an overview of the chemical composition, bioavailability and bioaccessibility of krill oil, as well as the mechanisms of action, classic and non-conventional extraction techniques, health benefits and current applications of this marine crustacean.

A review of pharmacological and pharmacokinetic properties of Forsythiaside A.

Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Forsythiae Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a widely used Chinese medicinal herb in clinic for its extensive pharmacological activities. Forsythiaside A is the main active index component isolated from Forsythiae Fructus and possesses prominent bioactivities. Modern pharmacological studies have confirmed that Forsythiaside A exhibits significant activities in treating various diseases, including inflammation, virus infection, neurodegeneration, oxidative stress, liver injury, and bacterial infection. In this review, the pharmacological activities of Forsythiaside A have been comprehensively reviewed and summarized. According to the data, Forsythiaside A shows remarkable anti-inflammation, antivirus, neuroprotection, antioxidant, hepatoprotection, and antibacterial activities through regulating multiple signaling transduction pathways such as NF-κB, MAPK, JAK/STAT, Nrf2, RLRs, TRAF, TLR7, and ER stress. In addition, the toxicity and pharmacokinetic properties of Forsythiaside A are also discussed in this review, thus providing a solid foundation and evidence for further studies to explore novel effective drugs from Chinese medicine monomers.

Pharmacokinetics-based chronoefficacy of Fuzi against chronic kidney disease.

OBJECTIVES: Identifying drugs with time-varying efficacy or toxicity, and understanding the underlying mechanisms would help to improve treatment efficacy and reduce adverse effects. In this study, we uncovered that the therapeutic effect of Fuzi (the lateral root of Aconitum carmichaelii Debeaux) depended on the dosing time in mice with adenine-induced chronic kidney disease (CKD). METHODS: The Fuzi efficacy was determined by biomarker measurements [i.e. plasma creatinine (CRE), blood urea nitrogen (BUN) and urinary N-acetyl-ß-D-glucosaminidase (NAG)], as well as inflammation, fibrosis and histological analyses. Circadian regulation of Fuzi pharmacokinetics and efficacy was evaluated using brain and muscle Arnt-like protein-1 (Bmal1)-deficient (Bmal1-/-) mice. KEY FINDINGS: The Fuzi efficacy was higher when the drug was dosed at ZT10 and was lower when the drug was dosed at other times (ZT2, ZT6, ZT14, ZT18 and ZT22) according to measurements of plasma CRE, BUN and urinary NAG. Consistently, ZT10 (5 PM) dosing showed a stronger protective effect on the kidney (i.e. less extensive tubular injury) as compared to ZT22 (5 AM) dosing. This was supported by lower levels of inflammatory and fibrotic factors (IL-1ß, IL-6, Tnf-α, Ccl2, Tgfb1 and Col1a1) at ZT10 than at ZT22. Pharmacokinetic analyses showed that the area under the curve (AUC) values (reflective of systemic exposure) and renal distribution of aconitine, hypaconitine and mesaconitine (three putative active constituents) for Fuzi dosing at ZT10 were significantly higher than those for herb dosing at ZT22, suggesting a role of circadian pharmacokinetics in Fuzi chronoefficacy. Drug efficacy studies confirmed that aconitine, hypaconitine and mesaconitine possessed a kidney-protecting effect. In addition, genetic knockout of Bmal1 in mice abolished the time-dependency of Fuzi pharmacokinetics and efficacy. This reinforced the existence of chronoefficacy for Fuzi and supported the role of circadian pharmacokinetics in Fuzi chronoefficacy. CONCLUSIONS: The efficacy of Fuzi against CKD depends on the dosing time in mice, which is associated with circadian pharmacokinetics of the three main active constituents (i.e. aconitine, hypaconitine and mesaconitine). These findings highlight the relevance of dosing time in the therapeutic outcomes of herbal medicines.

Comparison of plasma and pulmonary availability of chlorogenic acid, forsythiaside A and baicalin after intratracheal and intravenous administration of Shuang-Huang-Lian injection.

ETHNOPHARMACOLOGICAL RELEVANCE: The off-label nebulization of Shuang-Huang-Lian (SHL) injection is often utilized to treat respiratory tract infections in China. However, the pulmonary biopharmaceutics of SHL was generally unknown, limiting the rational selection of therapeutic dose and dose frequency. AIM OF THE STUDY: To characterize the size distribution of nebulized aerosols and to compare the pharmacokinetics and the lung distribution of three chemical makers of SHL, chlorogenic acid (CHA), forsythiaside A (FTA) and baicalin (BC), after intratracheal and intravenous administration of SHL to rats. MATERIALS AND METHODS: The droplet size distribution profiles over nebulization process were dynamically monitored using a laser diffraction method whereas the levels of CHA, FTA and BC in plasma, lung tissues and bronchoalveolar lavage fluids (BALF) were determined by a validated LC-MS/MS assay. The pulmonary anti-inflammatory efficacy was evaluated using a lipopolysaccharide (LPS) induced lung inflammation model as indicated by the level of tumor necrosis factor-α (TNF-α) in BALF. RESULTS: The nebulization of SHL showed good inhalability and allowed the aerosols to reach the upper or lower respiratory tract dependent on the performance of selected nebulizers. Following intratracheal administration of SHL at different doses, CHA, FTA and BC were absorbed into the bloodstream with the mean absorption time being 67.5, 63.5 and 114 min, respectively, rendering mean absolute bioavailabilities between 42.4% and 61.4% roughly independent of delivered dose. Relative to the intravenous injection, the intrapulmonary delivery increased the lung-to-plasma concentration ratios of CHA, FTA and BC by more than 100 folds and markedly improved the lung availability by 563-676 folds, leading to enhanced and prolonged lung retention. The production of TNF-α in BALF was decreased by ~50% at an intratracheal dose of 125 µL/kg SHL to LPS-treated mice. CONCLUSION: The nebulization delivery of SHL is a promising alternative to the intravenous injection for the treatment of respiratory tract infections.

Pharmacokinetic-pharmacodynamic modeling analysis and anti-inflammatory effect of Wangbi capsule in the treatment of adjuvant-induced arthritis.

Clinically, Wangbi Capsule (WBC) is widely used in the treatment of Rheumatoid arthritis (RA) because of its remarkable therapeutic effect. To reveal the mechanism, a pharmacokinetic-pharmacodynamic (PK-PD) model was developed for the first time to assess the relationship between time-concentration (dose)-effect. Freund's Complete Adjuvant was used to induce the adjuvant-induced arthritis model. Multi-indices were used to evaluate the therapeutic effect and an S-Imax PK-PD model was established based on the concentrations of osthole, 5-O-methylvisamminoside, cimifugin, albiflorin, paeoniflorin and icariin and the levels of interleukin-1ß and prostaglandin E2 using a two-compartment PK model together with a PD model with an effect-site compartment. The results suggest that WBC can treat RA by regulating the levels of prostaglandin E2 and interleukin-1ß. For the PK-PD model, the parameters indicated that WBC had a large safety margin and all six bioactive ingredients of WBC have therapeutic effects on RA. Among them icariin, osthole and 5-O-methylvisamminoside may be the main effective substances. This study provided a scientific basis for further study of population pharmacokinetics / population pharmacodynamics (PPK/PPD), to develop a reasonable administration plan and improve individualized drug therapy.

Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids.

Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.

Improving in vitro bioaccessibility and bioactivity of carnosic acid using a lecithin-based nanoemulsion system.

As a phenolic terpenoid, carnosic acid (CA) mainly exists in rosemary, which can be effectively used for the treatment of degenerative and chronic diseases by taking advantage of its health-promoting bioactivities. However, the low solubility and dissolution of CA in aqueous solutions at ambient and body temperatures result in low stability and bioaccessibility during the digestion process, which limits its application scope in the functional foods industry. In this regard, a lecithin based nanoemulsion system (CA-NE) is employed in the present work to enhance the bioaccessibility and bioactivities of CA. It is revealed that the CA-NE under investigation exhibits high loading capacity (2.80 ± 0.15%), small particle size (172.0 ± 3.5 nm) with homogeneous particle distribution (polydispersity index (PDI) of 0.231± 0.025) and high repulsive force (zeta potential = -57.2 ± 0.24 mV). More importantly, the bioaccessibility of CA-NE is improved by 2.8-fold compared to that of CA in MCT oil. In addition, the cellular antioxidant assay (CAA) and cellular uptake study of the CA-NE in HepG2 cell models demonstrate a longer endocytosis process, suggesting the well-controlled release of CA from CA-NE. Furthermore, an improved anti-inflammatory activity was evaluated via the inhibition of the pro-inflammatory cytokines, nitric oxide (NO) and TNF-α production in LPS-stimulated RAW 264.7 macrophage cells. The results clearly demonstrated a promising application of CA-NE as a functional food.

Phytochemical Characterization, In Vitro Anti-Inflammatory, Anti-Diabetic, and Cytotoxic Activities of the Edible Aromatic Plant; Pulicaria jaubertii.

Pulicaria jaubertii is a medicinal herb that alleviates inflammations and fever. Chromatographic separation, phytochemical characterization, and in vitro biological activities of the plant n-hexane extract were conducted for the first time in this study. Six compounds were isolated for the first time from the n-hexane fraction of Pulicaria jaubertii aerial parts and were identified on the bases of NMR and MS analyses as pseudo-taraxaterol (1), pseudo-taraxasterol acetate (2), 3ß-acetoxytaraxaster-20-en-30-aldehyde (3), calenduladiol-3-O-palmitate (4), stigmasterol (5), and α-tocospiro B (6). Compound (6) was a rare tocopherol-related compound and was isolated for the first time from family Asteraceae, while compound (3) was isolated for the first time from genus Pulicaria. The total alcoholic extract and n-hexane fraction were tested for their anti-inflammatory, antidiabetic, and cytotoxic activities. The n-hexane fraction has dose dependent red blood cells (RBCs) membrane stabilization and inhibition of histamine release activities with IC50: 60.8 and 72.9 µg/mL, respectively. As antidiabetic activity, the alcoholic extract exerted the most inhibition on the activity of yeast α-glucosidase, with an IC50: 76.8 µg/mL. The n-hexane fraction showed cytotoxic activity against hepatocarcinoma (HepG-2), breast carcinoma (MCF-7), and prostate carcinoma (PC-3) cell lines with IC50: 51.8, 90.8 and 62.2 µg/mL, respectively. In conclusion, the anti-inflammatory effect of Pulicaria jaubertii might be attributed to the triterpenoid constituents of the n-hexane extract of the plant.

Lupeol and its derivatives as anticancer and anti-inflammatory agents: Molecular mechanisms and therapeutic efficacy.

Lupeol is a natural triterpenoid that widely exists in edible fruits and vegetables, and medicinal plants. In the last decade, a plethora of studies on the pharmacological activities of lupeol have been conducted and have demonstrated that lupeol possesses an extensive range of pharmacological activities such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. Pharmacokinetic studies have indicated that absorption of lupeol by animals was rapid despite its nonpolar characteristics, and lupeol belongs to class II BCS (biopharmaceutics classification system) compounds. Moreover, the bioactivities of some isolated or synthesized lupeol derivatives have been investigated, and these results showed that, with modification to C-3 or C-19, some derivatives exhibit stronger activities, e.g., antiprotozoal or anticancer activity. This review aims to summarize the advances in pharmacological and pharmacokinetic studies of lupeol in the last decade with an emphasis on its anticancer and anti-inflammatory activities, as well as the research progress of lupeol derivatives thus far, to provide researchers with the latest information, point out the limitations of relevant research at the current stage and the aspects that should be strengthened in future research.

Atractylenolides, essential components of Atractylodes-based traditional herbal medicines: Antioxidant, anti-inflammatory and anticancer properties.

The rhizome of the plant Atractylodes macrocephala Koidz is the major constituent of the Traditional Chinese Medicine Baizhu, frequently used to treat gastro-intestinal diseases. Many traditional medicine prescriptions based on Baizhu and the similar preparation Cangzhu are used in China, Korea and Japan as Qi-booster. These preparations contain atractylenolides, a small group of sesquiterpenoids endowed with antioxidant and anti-inflammatory properties. Atractylenolides I, II and III also display significant anticancer properties, reviewed here. The capacity of AT-I/II/IIII to inhibit cell proliferation and to induce cancer cell death have been analyzed, together with their effects of angiogenesis, metastasis, cell differentiation and stemness. The immune-modulatory properties of ATs are discussed. AT-I has been tested clinically for the treatment of cancer-induced cachexia with encouraging results. ATs, alone or combined with cytotoxic drugs, could be useful to treat cancers or to reduce side effects of radio and chemotherapy. Several signaling pathways have been implicated in their multi-targeted mechanisms of action, in particular those involving the central regulators TLR4, NFκB and Nrf2. A drug-induced reduction of inflammatory cytokines production (TNFα, IL-6) also characterizes these molecules which are generally weakly cytotoxic and well tolerated in vivo. Inhibition of Janus kinases (notably JAK2 and JAK3 targeted by AT-I and AT-III, respectively) has been postulated. Information about their metabolism and toxicity are limited but the long-established traditional use of the Atractylodes and the diversity of anticancer effects reported with AT-I and AT-III should encourage further studies with these molecules and structurally related natural products.

Carboxymethyl chitosan microspheres loaded hyaluronic acid/gelatin hydrogels for controlled drug delivery and the treatment of inflammatory bowel disease.

A major drawback of oral treatment of inflammatory bowel disease (IBD) is the non-specific distribution of drugs during long-term treatment. Despite its effectiveness as an anti-inflammatory drug, curcumin (CUR) is limited by its low bioavailability in IBD treatment. Herein, a pH-sensitive composite hyaluronic acid/gelatin (HA/GE) hydrogel drug delivery system containing carboxymethyl chitosan (CC) microspheres loaded with CUR was fabricated for IBD treatment. The composition and structure of the composite system were optimized and the physicochemical properties were characterized using infrared spectroscopy, X-ray diffraction, swelling, and release behavior studies. In vitro, the formulation exhibited good sustained release property and the drug release rate was 65% for 50 h. In vivo pharmacokinetic experiments indicated that high level of CUR was maintained in the colon tissue for more than 24 h; it also played an anti-inflammatory role by evaluating the histopathological changes through hematoxylin and eosin (H&E), myeloperoxidase (MPO), and immunofluorescent staining. Additionally, the formulation substantially inhibited the level of the main pro-inflammatory cytokines of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secreted by macrophages, compared to the control group. The pharmacodynamic experiment showed that the formulation group of CUR@gels had the best therapeutic effect on colitis in mice. The composite gel delivery system has potential for the effective delivery of CUR in the treatment of colitis. This study also provides a reference for the design and preparation of a new oral drug delivery system with controlled release behavior.

Matrine: A review of its pharmacology, pharmacokinetics, toxicity, clinical application and preparation researches.

ETHNOPHARMACOLOGICAL RELEVANCE: "Dogel ebs" was known as Sophora flavescens Ait., which has been widely utilized in the clinical practice of traditional Chinese Mongolian herbal medicine for thousands of years. Shen Nong's Materia Medica (Shen Nong Ben Cao Jing in Chinese pinyin) recorded that it is bitter in taste and cold in nature with the effect of clearing heat and eliminating dampness, insecticide, diuresis. Due to its extensive application in the fields of ethnopharmacological utilization, the pharmaceutical researches of Sophora flavescens Ait.s keeps deepening. Modern pharmacological studies have exhibited that matrine, which is rich in this traditional herbal medicine, mediates its main biological properties. AIMS OF THE REVIEW: This review aimed at summarizing the latest and comprehensive information of matrine on the pharmacology, pharmacokinetics, toxicity, clinical application and preparation researches to explore the therapeutic potential of this natural ingredient. In addition, outlooks and perspective for possible future researches that related are also discussed. MATERIALS AND METHODS: Related information concerning matrine was gathered from the internet database of Google scholar, Pubmed, ResearchGate, Web of Science and Wiley Online Library with the keywords including "matrine", "pharmacology", "toxicology" and "pharmacokinetics", "clinical application", etc. RESULTS: Based on literatures, matrine has a variety of pharmacological effects, including anti-cancer, anti-inflammatory, anti-microbial, detoxification and so on. Nevertheless, there are still some doubts about it due to the toxicity and questionable bioavailability that does exist. CONCLUSIONS: Future researches directions probably include elucidate the mechanism of its toxicity and accurately tracing the in vivo behavior of its drug delivery system. Without doubt, integration of toxicity and efficiency and structure modification based on it are also pivotal methods to enhance pharmacological activity and bioavailability.