Dibenzocyclooctadiene lignans from the family Schisandraceae: A review of phytochemistry, structure-activity relationship, and hepatoprotective effects.

Liver injury is a common pathological process characterized by massive degeneration and abnormal death of liver cells. With increase in dead cells and necrosis, liver injury eventually leads to nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and even hepatocellular carcinoma (HCC). Consequently, it is necessary to treat liver injury and to prevent its progression. The drug Bicylol is widely employed in China to treat chronic hepatitis B virus (HBV) and has therapeutic potential for liver injury. It is the derivative of dibenzocyclooctadiene lignans extracted from Schisandra chinensis (SC). The Schisandraceae family is a rich source of dibenzocyclooctadiene lignans, which possesses potential liver protective activity. This study aimed to comprehensively summarize the phytochemistry, structure-activity relationship and molecular mechanisms underlying the liver protective activities of dibenzocyclooctadiene lignans from the Schisandraceae family. Here, we had discussed the analysis of absorption or permeation properties of 358 compounds based on Lipinski's rule of five. So far, 358 dibenzocyclooctadiene lignans have been reported, with 37 of them exhibited hepatoprotective effects. The molecular mechanism of the active compounds mainly involves antioxidative stress, anti-inflammation and autophagy through Kelch-like ECH-associating protein 1/nuclear factor erythroid 2 related factor 2/antioxidant response element (Keap1/Nrf2/ARE), nuclear factor kappa B (NF-кB), and transforming growth factor ß (TGF-ß)/Smad 2/3 signaling pathways. This review is expected to provide scientific ideas for future research related to developing and utilizing the dibenzocyclooctadiene lignans from Schisandraceae family.

Phytohormone Response of Drought-Acclimated Illicium difengpi (Schisandraceae).

Illicium difengpi (Schisandraceae), which is an endemic, medicinal, and endangered species found in small and isolated populations that inhabit karst mountain areas, has evolved strategies to adapt to arid environments and is thus an excellent material for exploring the mechanisms of tolerance to severe drought. In experiment I, I. difengpi plants were subjected to three soil watering treatments (CK, well-watered treatment at 50% of the dry soil weight for 18 days; DS, drought stress treatment at 10% of the dry soil weight for 18 days; DS-R, drought-rehydration treatment at 10% of the dry soil weight for 15 days followed by rewatering to 50% of the dry soil weight for another 3 days). The effects of the drought and rehydration treatments on leaf succulence, phytohormones, and phytohormonal signal transduction in I. difengpi plants were investigated. In experiment II, exogenous abscisic acid (ABA, 60 mg L-1) and zeatin riboside (ZR, 60 mg L-1) were sprayed onto DS-treated plants to verify the roles of exogenous phytohormones in alleviating drought injury. Leaf succulence showed marked changes in response to the DS and DS-R treatments. The relative concentrations of ABA, methyl jasmonate (MeJA), salicylic acid glucoside (SAG), and cis-zeatin riboside (cZR) were highly correlated with relative leaf succulence. The leaf succulence of drought-treated I. difengpi plants recovered to that observed with the CK treatment after exogenous application of ABA or ZR. Differentially expressed genes involved in biosynthesis and signal transduction of phytohormones (ABA and JA) in response to drought stress were identified by transcriptomic profiling. The current study suggested that the phytohormones ABA, JA, and ZR may play important roles in the response to severe drought and provides a preliminary understanding of the physiological mechanisms involved in phytohormonal regulation in I. difengpi, an endemic, medicinal, and highly drought-tolerant plant found in extremely small populations in the karst region of South China.

Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products.

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is 'external' to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the 'real' substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts.

The Journey of Schinortriterpenoid Total Syntheses.

Plants in the Schisandraceae family are important components of the traditional Chinese herbal medicines and are often used to treat various illnesses. Therefore, these Schisandraceae plants are valuable sources for the discovery of new chemical entities for novel therapeutic development. Considerable progress has been made in the identification of bioactive and structurally novel triterpenoids from the Schisandraceae family in the past two decades. In particular, Sun and co-workers have successfully isolated over 100 nortriterpenoids from the Schisandraceae family. Some of these nortriterpenoids have strong inhibitory activities toward hepatitis, tumors, and HIV-1. However, the natural scarcity of these nortriterpenoids in the Schisandraceae plants has hampered their isolation and further biomedical development, and their biosynthesis has not been fully elucidated. It is therefore important and urgent to develop efficient and streamlined total syntheses of these medicinally important nortriterpenoids. Such syntheses will provide sufficient materials for detailed biological studies as well as new synthetic analogues and probe molecules to improve their biological functions and elucidate their mode of actions. However, because of their structural novelty and complexity, the total syntheses of these nortriterpenoid natural products present a significant challenge for synthetic chemists, despite the progress made in organic synthesis, particularly total synthesis, in the 20th century and since the beginning of the 21st century. New synthetic methodologies and strategies therefore need to be invented and developed to facilitate the total syntheses of these nortriterpenoid natural products. With this in mind, our group has spent the last 15 years, ever since the isolation of micrandilactone A (1) by Sun and co-workers in 2003 ( Sun et al. Org. Lett. 2003 , 5 , 1023 - 1026 ), working on synthetic studies with a view to developing methods and strategies for the total syntheses of schinortriterpenoids. Enabling methods such as a thiourea/Pd-catalyzed alkocycarbonylative annulation and a thiourea/Co-catalyzed Pauson-Khand reaction have been developed under these circumstances to form the key ring systems and stereocenters of these complex target molecules. These methodological advances have led us to the first total syntheses of schindilactone A (2), lancifodilactone G acetate (6a), 19-dehydroxyarisandilactone A (9), and propindilactone G (10) with diverse structural features via a branching-oriented strategy. The chemistry developed during our total synthesis campaign has not only helped us to deal with various challenges encountered in the syntheses of the four target molecules, but has also opened up new avenues for synthesizing other naturally occurring schinortriterpenoids and their derivatives, which will likely result in molecules with improved biological functions and tool compounds to enable elucidation of their mechanism of actions or potential cellular targets. This Account highlights the chemistry evolution of our schinortriterpenoid syntheses.

Effect of Illicium verum or Eucommia ulmoides leaf extracts on the anti-stress ability, and mRNA and protein expression of Nrf2 and TNF-α in Duroc × Landrace × Yorkshire and Chinese native Licha-black nursery piglets.

Plant extracts are considered to be an effective alternative to antibiotics in response to weaning stress in piglets. This study evaluated the effect of Illicium verum extracts (IVE) or Eucommia ulmoides leaf extracts (ELE) on growth performance, serum and liver antioxidant ability of nursery piglets, as well as the difference of IVE and ELE on Duroc × Landrace × Yorkshire (DLY) and Chinese native Licha-black (LCB) piglets. A total of 96 nursery piglets (48 DLY and 48 LCB piglets) with an average body weight of 11.22 ± 0.32 kg were randomly divided into four treatments in a 2 × 4 factorial design. Each treatment had four replicates with 3 DLY and 3 LCB piglets per replicate respectively. Treatments included: basal diet, basal diet + 500 mg/kg IVE, basal diet + 250 mg/kg ELE and basal diet + 50 mg/kg chlortetracycline (CHL). All piglets were housed individually for the 42 days trial period after 7 days adaptation. Results showed that there were significant interactions (p < .05) between piglets species and dietary treatments in average daily gain (ADG) and feed efficiency, serum and hepatic glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), hepatic integral optical density (IOD) of α-tumour necrosis factor (TNF-α), hepatic relative mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/TNF-α and protein expression of TNF-α. Regardless of piglets species, supplementation with IVE and ELE increased (p < .05) ADG and feed efficiency, T-SOD and GSH-Px in serum and liver, hepatic IOD of Nrf2, hepatic mRNA and protein expression of Nrf2/TNF-α. However, CHL treatment resulted in lower (p < .05) serum GSH-Px and hepatic mRNA and protein expression of Nrf2/TNF-α, and higher hepatic MDA and IOD of TNF-α. Compared to LCB, DLY piglets had higher (p < .05) ADG and feed efficiency, serum and hepatic MDA, and protein expression of TNF-α, but lower (p < .05) ADFI, liver index, serum and hepatic GSH-Px, hepatic IOD of TNF-α, mRNA expressions of Nrf2/TNF-α were observed. In conclusion, Illicium verum (500 mg/kg) and Eucommia ulmoides leaf (250 mg/kg) extracts can increase the growth performance and antioxidant ability of DLY and LCB piglets, while chlortetracycline produces undesirable side-effects on the antioxidant ability of DLY and LCB piglets. Illicium verum and Eucommia ulmoides leaf extracts produced different antioxidant effects in DLY and LCB piglets with the Chinese native Licha-black pig responding better than Duroc × Landrace × Yorkshire.

The largest early-diverging angiosperm family is mostly pollinated by ovipositing insects and so are most surviving lineages of early angiosperms.

Insect pollination in basal angiosperms is assumed to mostly involve 'generalized' insects looking for food, but direct observations of ANITA grade (283 species) pollinators are sparse. We present new data for numerous Schisandraceae, the largest ANITA family, from fieldwork, nocturnal filming, electron microscopy, barcoding and molecular clocks to infer pollinator/plant interactions over multiple years at sites throughout China to test the extent of pollinator specificity. Schisandraceae are pollinated by nocturnal gall midges that lay eggs in the flowers and whose larvae then feed on floral exudates. At least three Schisandraceae have shifted to beetle pollination. Pollination by a single midge species predominates, but one species was pollinated by different species at three locations and one by two at the same location. Based on molecular clocks, gall midges and Schisandraceae may have interacted since at least the Early Miocene. Combining these findings with a review of all published ANITA pollination data shows that ovipositing flies are the most common pollinators of living representatives of the ANITA grade. Compared to food reward-based pollination, oviposition-based systems are less wasteful of plant gametes because (i) none are eaten and (ii) female insects with herbivorous larvae reliably visit conspecific flowers.

Total Synthesis of the Schisandraceae Nortriterpenoid Rubriflordilactone†A.

Full details of the total synthesis of the Schisandraceae nortriterpenoid natural product rubriflordilactone A are reported. Palladium- and cobalt-catalyzed polycyclizations were employed as key strategies to construct the central pentasubstituted arene from bromoendiyne and triyne precursors. This required the independent assembly of two AB ring aldehydes for combination with a common diyne component. A number of model systems were explored to investigate these two methodologies, and also to establish routes for the installation of the challenging benzopyran and butenolide rings.

Triterpenoids from the Schisandraceae family: an update.

Several significant advances in the field of phytochemistry were made between 2008 and 2014 because of the high level of interest in Schisandraceae triterpenoids. In addition to a dramatic increase in the number of newly identified triterpenoids, the first complete synthesis of a schinortriterpenoid was accomplished. There has also been substantial progress in investigations of biological activity and mechanism of action. In this update, we review more than 250 new triterpenoids and describe their structures, classifications, biogenetic pathways, syntheses, and bioactivities.

Schisandrosides A-D, Dibenzocyclooctadiene Lignan Glucosides from the Roots of Schisandra chinensis.

Four new dibenzocyclooctadiene lignan glucosides, schisandrosides A-D (1-4), as well as two known rare nortriterpenoids, micrandilactone C (5) and propindilactone Q (6), were isolated from the roots of Schisandra chinensis BAILLON (Schisandraceae). The structure of compounds 1-4 were elucidated by physical and spectroscopic data interpretation. To the best of our knowledge, schisandrosides A-D (1-4) represent the first example of a dibenzocyclooctadiene lignan glycoside.

Mitochondrial decay in ageing: 'Qi-invigorating' schisandrin B as a hormetic agent for mitigating age-related diseases.

1. The mitochondrial free radical theory of ageing (MFRTA) proposes a primary role for mitochondrial reactive oxygen species (ROS) in the ageing process. The reductive hot spot hypothesis of mammalian ageing serves as a supplement to the MFRTA by explaining how the relatively few cells that have lost oxidative phosphorylation capacity due to mitochondrial DNA mutations can be toxic to the rest of the body and result in the development of age-related diseases. 2. Schisandrin B (SchB), which can induce both a glutathione anti-oxidant and a heat shock response via redox-sensitive signalling pathways, is a hormetic agent potentially useful for increasing the resistance of tissues to oxidative damage. The enhanced cellular/mitochondrial anti-oxidant status and heat shock response afforded by SchB can preserve the structural and functional integrity of mitochondria, suggesting a potential role for SchB in ameliorating age-related diseases. 3. Future studies will focus on investigating whether SchB can produce the hormetic response in humans.

[Ethno-pharmacological investigation of Schisandraceae plants in China].

OBJECTIVE: To investigate and arrange the ethno-pharmacological information of Schisandraceae plants in China. METHOD: The information was obtained by literature search, specimen inspection, field resource investigation and samples collection. RESULT: Twenty-six Schisandraece plants (inlcuding 4 varieties) have been used as folk medicines in different regions of China, the identical medicinal parts of different species in one genus show the similar usage, action and indications, and different medicinal parts with different administrated ways show different action and indications. CONCLUSION: The results provide reliable information for resource development and comprehensive utilization of Schisandraece plant resource in China.

Schisandraceae triterpenoids: A review of phytochemistry, bioactivities and synthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Schisandraceae family have a rich and medicinal history dating back to ancient times. Many of them are used as folk medicine in the treatment of chronic coughs, asthma, nocturnal emission, spontaneous sweating, night sweats, palpitation, insomnia and thirst. AIM OF THE REVIEW: The current review is carried out on triterpenoids from the Schisandraceae family, aiming to comprehensively summarize their phytochemistry, pharmacology and synthesis and provide new insights to the chemical and pharmacological study and rational utilization on medicinal plants of the Schisandarceae family. MATERIALS AND METHODS: The information was searched from the scientific literature published from June 2014 to November 2021 on the online databases (including PubMed, CNKI, Elsevier, SciFinder and Web of Science) and other bibliography (e.g. the Chinese Pharmacopoeia, 2020 edition, Chinese herbal books). The scientific literature related to phytochemistry, pharmacology, biological activites and synthesis of triterpenoids from the Schisandraceae family was gathered. RESULTS: From June 2014 to November 2021, there were approximately 211 novel triterpenoids isolated and identified from 18 species of the Schisandraceae family. These compounds exhibit tremendous diversity in their structures, and some of them possess promising pharmacological activities, including anti-viral, anti-tumor, anti-inflammatory, hepatoprotective, immunosuppressive activities and neuroprotective effects. In the attempt to synthesize active compounds, the total synthesis of 13 schinortriterpenoids belonging to five structural types was successfully completed. CONCLUSIONS: Studies of triterpenoids from the Schisandraceae family are well documented in this review (from June 2014 to November 2021), and it is also well acknowledged that they are valuable resources with medicinal efficacy. However, relevant pharmacological studies are limited to in vitro tests, and data from in vivo studies and toxicology are lacking or unavailable. Fortunately, there is growing interest in the synthesis of active compounds, which should serve as an approach for accessing active compounds to develop in vivo or toxicity studies, with a view of clarifying their in vitro and vivo mechanisms for more effective and safe natural drugs.

[Metabonomic phenotype of "formula corresponding to pattern types" based on "qi and yin deficiency pattern" of myocardial ischemia rat model].

In order to explore the scientific connotation of "Fangzhengduiying (formula corresponding to pattern types)", "Qiyinliangxuzheng (Qi and Yin deficiency pattern)" of myocardial ischemia rat model and GC-TOF/MS based metabonomic method were used for comparing the effects of Sheng-mai injection, Salvia injection and propranolol in the present study. After data processing and pattern recognition, Sheng-mai injection showed better efficacy than the other two drugs in accordance with not only visual observation from PLS-DA scores plots but also the number of abnormal endogenous compounds restored to the normal level. Further studies showed that Sheng-mai injection could normalize the level of plasma endothelin-1, the index related to cardiovascular diseases and sleep disorders, which verified the results of metabonomics. Finally, the regulated metabolites and related metabolic pathways were analyzed, and it was supposed that the effects of Sheng-mai injection involved in the alternation of energy metabolism, lipid metabolism, amino acids metabolism, and so on. These findings provided scientific evidence to Shengmai "Fang" used for "Qi and Yin deficiency pattern" correspondingly, indicating that metabonomics has great potential in traditional Chinese medical research, which provides a novel approach and way to modernization of traditional Chinese medicine.

Mimicking oxidative radical cyclizations of lignan biosynthesis using redox-neutral photocatalysis.

Oxidative cyclizations create many unique chemical structures that are characteristic of biologically active natural products. Many of these reactions are catalysed by 'non-canonical' or 'thwarted' iron oxygenases and appear to involve long-lived radicals. Mimicking these biosynthetic transformations with chemical equivalents has been a long-standing goal of synthetic chemists but the fleeting nature of radicals, particularly under oxidizing conditions, makes this challenging. Here we use redox-neutral photocatalysis to generate radicals that are likely to be involved in the biosynthesis of lignan natural products. We present the total syntheses of highly oxidized dibenzocyclooctadienes, which feature densely fused, polycyclic frameworks that originate from a common radical progenitor. We show that multiple factors control the fate of the proposed biosynthetic radicals, as they select between 5- or 11-membered ring cyclizations and a number of different terminating events. Our syntheses create new opportunities to explore the medicinal properties of these natural products, while shedding light on their biosynthetic origin.

[Effective components against HIV-1 replicative enzymes isolated from plants].

Plant active components characterized of many different structures and activities on multiple targets, have made them to be the important sources of inhibitors on HIV-1. For finding leading compounds with new structure against HIV-1, three key HIV-1 replicative enzymes (reverse transcriptase, protease and integrase) were used as screening models. The in vitro activities of 45 plant derived components isolated from Schisandraceae, Rutaceae and Ranunculaceae were reported. Within twelve triterpene components isolated, eight compounds were found to inhibit HIV-1 protease, in these eight active compounds, kadsuranic acid A (7) and nigranoic acid (8), inhibited both HIV-1 protease and integrase; Among fifteen lignans, meso-dihydroguaiaretic acid (15) and kadsurarin (16) were active on HIV-1 reverse transcriptase, and 4, 4-di(4-hydroxy-3-methoxyphenly)-2, 3-dimethylbutanol (13) active on HIV-1 integrase. All of the six alkaloids, seven flavones, and five others compounds were not active or only with low activities against HIV-1 replicative enzymes. Further studies of the triterpene components showing strong inhibitory activities on HIV-1 were warranted.

[Schisandrin B prevents doxorubicin-induced cardiotoxicity in rabbits].

OBJECTIVE: To study the effect of dexrazoxane in preventing doxorubicin-induced cardiotoxicity in rabbit-models and its mechanism. METHODS: Thirty one New Zealand white rabbits were randomly divided into two groups, doxorubicin (DOX) group and doxorubicin + dexrazoxane group. The cardiotoxicity was assessed by measuring serum superoxide dismutase (SOD), malondialdehyde (MDA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP), left ventricular ejection function (LVEF), and left ventricular fractional shortening (LVFS), before and 4 and 10 weeks after intervention. Pathological changes in cardiac tissues and the apoptosis of myocardial cells were examined at the end of the experiment. Results Doxorubicin increased serum MDA, cTnI and BNP and decreased SOD, LVEF and LVFS (P < 0.05). Dexrazoxane (DEX) inhibited the increase of MDA, cTnI and BNP, and the decrease of LVEF and LVFS (P < 0.05). The rabbits treated with doxorubicin + dexrazoxane had slighter pathological changes in myocardium and apoptotic myocardial cells than those treated with DOX. CONCLUSION: Dexrazoxane prevents doxorubicin-induced cardiotoxicity through decreasing oxygen free radical production, cutting down lipid peroxidation, and depressing cardiocyte apoptosis.

Characteristic and Phylogenetic Analysis of the Complete Chloroplast Genomes of Three Medicinal Plants of Schisandraceae.

Schisandra chinensis, which has a high development value, has long been used as medicine. Its mature fruits (called Wuweizi in Chinese) have long been used in the famous traditional Chinese medicine (TCM) recorded in the "Chinese Pharmacopoeia." Chloroplasts (CP) are the highly conserved primitive organelles in plants, which can serve as the foundation for plant classification and identification. This study introduced the structures of the CP genomes of three Schisandraceae species and analyzed their phylogenetic relationships. Comparative analyses on the three complete chloroplast genomes can provide us with useful knowledge to identify the three plants. In this study, approximately 5 g fresh leaves were harvested for chloroplast DNA isolation according to the improved extraction method. A total of three chloroplast DNAs were extracted. Afterwards, the chloroplast genomes were reconstructed using denovo combined with reference-guided assemblies. General characteristics of the chloroplast genome and genome comparison with three Schisandraceae species was analyzed by corresponding software. The total sizes of complete chloroplast genomes of S. chinensis, S. sphenanthera, and Kadsura coccinea were 146875 bp, 146842 bp, and 145399 bp, respectively. Altogether, 124 genes were annotated, including 82 protein-coding genes, 34 tRNAs, and 8 rRNAs of all 3 species. In SSR analysis, only S. chinensis was annotated to hexanucleotides. Moreover, comparative analysis of chloroplast Schisandraceae genome sequences revealed that the gene order and gene content were slightly different among Schisandraceae species. Finally, phylogenetic trees were reconstructed, based on the genome-wide SNPs of 38 species. The method can be used to identify and differentially analyze Schisandraceae plants and offer useful information for phylogenetics as well as further studies on traditional medicinal plants.

Effect of Schisandrae Fructus on glycyrrhizin content in Kampo extracts containing Glycyrrhizae Radix used clinically in Japan.

Glycyrrhizae Radix is an important crude drug in Japan and is the most frequently prescribed drug in Kampo medicines for the treatment of a wide range of diseases. Glycyrrhizin (GL), the major active ingredient of Glycyrrhizae Radix, has various pharmacological actions but causes adverse effects such as pseudoaldosteronism. In a previous study, the GL content of shoseiryuto was found to be unexpectedly low, and Schisandrae Fructus in shoseiryuto reduced the pH value of the decoction and drastically decreased the extraction efficiency of GL from Glycyrrhizae Radix. In the present study, we investigated the extraction efficiency of GL from Glycyrrhizae Radix in decoctions comprising Glycyrrhizae Radix and five different fruit-derived crude drugs. Among the five fruit-derived crude drugs tested, Schisandrae Fructus markedly decreased both the pH value of the decoction and the extraction efficiency of GL. A comparison of the pH value of the decoction and the GL content of 12 Kampo prescriptions (containing at least Glycyrrhizae Radix and Schisandrae Fructus) showed that the GL content per daily dose was proportional to the compounding amount of Glycyrrhizae Radix, and that the extraction efficiency of GL from Glycyrrhizae Radix was strongly correlated with the pH value of the decoction. In addition, the pH value of the decoction was similar to the pH value documented in interview forms provided by pharmaceutical companies. These results suggested that the GL content in Glycyrrhizae Radix-containing Kampo products can be estimated from both the compounding amounts of Glycyrrhizae Radix and the pH value documented in their interview forms. Knowledge of GL content will help avoid adverse reactions due to Glycyrrhizae Radix.

Analgesic and anti-inflammatory effects and molecular mechanisms of Kadsura heteroclita stems, an anti-arthritic Chinese Tujia ethnomedicinal herb.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by failure of spontaneous resolution of inflammation. The stem of Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinal plant, which named Xuetong in folk, has long been used for the prevention and treatment of rheumatic and arthritic diseases. AIM OF THE STUDY: The analgesic and anti-inflammatory effects and the potential mechanisms behind such effects of KHS would be investigated by using different animal models. MATERIALS AND METHODS: The abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid and the tail-flick response induced by radiant heat stimulation were used to evaluate the analgesic effect of KHS. The number of abdominal writhing episodes of mice and the latency of tail-flick in rats were measured and recorded. In acute inflammatory models, the ear edema of mice was induced by applying xylene on the ear surface, while the paw edema of male and female rats was induced by subcutaneous injection of carrageenan into the right hind paws of animals. The carrageenan-induced paw swelling in rats were selected as an anti-acute inflammatory mechanism of KHS. Serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) were measured by ELISA, and protein expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by Western blot. RESULTS: The maximal tolerated single dose of KHS was determined to be 26 g/kg in both sexes of mice. Pharmacological studies showed that KHS at the dose of 200 mg/kg significantly prolonged the reaction time of rats to radiant heat stimulation and suppressed abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid. KHS at the dose of 200, 400, and 800 mg/kg, showed dose-dependent inhibition of xylene-induced ear swelling in mice. KHS at the dose of 100, 200, 400, and 800 mg/kg demonstrated dose- and time-dependent suppression of paw edema induced by subcutaneous injection of carrageenan in both all rats. Mechanistic studies revealed that the anti-inflammatory effect of KHS was associated with inhibition of the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α and effectively decreased the expression of COX and iNOS proteins in the carrageenan-injected rat serum, paw tissues and inflammatory exudates. The positive reference drug, rotundine at a dosage of 100 mg/kg and indomethacin at a dosage of 10 mg/kg were used in both mice and rat models. CONCLUSION: These results suggested that KHS has significant effects on analgesia and anti-inflammation with decreasing the pro-inflammation cytokines of IL-1ß, IL-6, and TNF-α and inhibiting the proteins expression of COX-2 and iNOS.

Dynamic evolution and phylogenomic analysis of the chloroplast genome in Schisandraceae.

Chloroplast genomes of plants are highly conserved in both gene order and gene content, are maternally inherited, and have a lower rate of evolution. Chloroplast genomes are considered to be good models for testing lineage-specific molecular evolution. In this study, we use Schisandraceae as an example to generate insights into the overall evolutionary dynamics in chloroplast genomes and to establish the phylogenetic relationship of Schisandraceae based on chloroplast genome data using phylogenomic analysis. By comparing three Schisandraceae chloroplast genomes, we demonstrate that the gene order, gene content, and length of chloroplast genomes in Schisandraceae are highly conserved but experience dynamic evolution among species. The number of repeat variations were detected, and the Schisandraceae chloroplast genome was revealed as unusual in having a 10 kb contraction of the IR due to the genome size variations compared with other angiosperms. Phylogenomic analysis based on 82 protein-coding genes from 66 plant taxa clearly elucidated that Schisandraceae is a sister to a clade that includes magnoliids, monocots, and eudicots within angiosperms. As to genus relationships within Schisandraceae, Kadsura and Schisandra formed a monophyletic clade which was sister to Illicium.