Xiaoli Gao

Phytochemical and pharmacological progress on the genus Syringa

AbstractGenus Syringa, belonging to the Oleaceae family, consists of more than 40 plant species worldwide, of which 22 species, including 18 endemic species, are found in China. Most Syringa plants are used in making ornaments and traditional medicines, whereas some are employed for construction or economic use. Previous studies have shown that extracts of Syringa plants mainly contain iridoids, lignans, and phenylethanoids that have antitumor, antihypertensive, anti-oxidant, and anti-inflammatory activities. This study reviews phytochemical and pharmacological progress on Syringa in the recent 20 years and discusses the future research prospects to provide a reference in further promotion and application of the genus. Graphical AbstractPhytochemical and pharmacological progress on the genus Syringa

Alkaloids from the tribe Bocconieae (papaveraceae): a chemical and biological review.

The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the isolation and identification of a variety of molecules, has shed light on the tribe. Among those molecules, isoquinoline alkaloids, and their antimicrobial, antifungal, and anti-inflammatory activities are especially noteworthy. This paper presents a comprehensive compilation of current research progress, with emphasis on the alkaloids and their distribution, phytochemical and pharmacological investigation, toxicity and side effects, related chemotaxonomy and future use prospects, and hopefully provides a valuable reference as an effort to promote further exploration and application of this tribe.

Chemical constituents with NO production inhibitory and cytotoxic activities from Litsea cubeba

A bioassay-guided fractionation of the roots and stems of Litsea cubeba led to the isolation of 14 constituents, including three new compounds, cubebanone (1), N-cis-3,4-methylenedioxycinnamoyl-3-methoxytyramine (2), and 9,9′-O-di-(E)-feruloyl-(+)-secoisolariciresinol (3), together with 11 known ones (4–14). Compounds 1, 4, and 8–11 showed obvious in vitro anti-inflammatory activities against NO production in LPS-induced murine microglial (BV-2) cell line and RAW 264.7 macrophages. A cytotoxic evaluation showed that 2, 3, and 5–8 exhibited considerable inhibition against the growth of hepatocyte carcinoma (HepG2) cell line. These findings are evidence, to some extent, for the traditional medicinal application of L. cubeba, especially as folk medicine in the treatment of inflammation-related diseases.

Lignans from the stem bark of Syringa pinnatifolia.

Four new lignans, alashinols A-D (1-4), a new hydrolysis product, alashinols E (5), and seven known analogues were isolated from the stem bark of Syringa pinnatifolia Hemsl. These new lignans were characterized using 1D and 2D NMR and MS data, and their absolute configurations were determined by experimental and calculated electronic circular dichroism and X-ray diffraction analyses. Alashinol B (2) exhibited two conformers that adopted an unusual unit cell packing. Anti-inflammatory evaluation revealed that compounds 1, 4, 6, and 8 showed moderate inhibition against NO production in lipopolysaccharide-induced macrophages RAW 264.7 cells with IC50 values range from 43.3-60.9μM, and 1 decreased the TNF-α and IL-6 level in a concentration-dependent manner at 40-160μM and exhibited considerable neuroprotective effect against the glutamate-induced injury in PC12 cell line. Analogues 3 and 9 showed protective effects against oxygen glucose deprivation/reoxygenation in H9c2 cells.

Anti-Inflammatory Effects of Boldine and Reticuline Isolated from Litsea cubeba through JAK2/STAT3 and NF-κB Signaling Pathways

The anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba were evaluated by using xylene-induced ear edema and carrageenan-induced paw edema in mice and rats. Our results demonstrated that intragastric administration with boldine and reticuline significantly mitigated ear weight in mice and decreased paw volume in rats. A combination administration of boldine (0.5 mg/kg) + reticuline (0.25 mg/kg) resulted in a potentiated inhibition in these two models. In parallel, boldine or reticuline reduce the infiltration of neutrophil leukocytes in rat paw tissue, respectively, and the combination of the two groups performed a better anti-inflammatory activity as shown in histopathologies. Boldine, reticuline, and their combination notably inhibited mRNA expressions of TNF-α, and IL-6 and reduced the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Beyond that, their combination also can reduce the phosphorylation levels of p65 and IκBα in the pathological tissues of animals, as observed by real-time PCR and western blot analyses, respectively. These findings indicate for the first time that boldine and reticuline have not only anti-inflammatory activity but also potential synergistic effects in vivo. The underlying mechanism may relate to the inhibition on the expression of pro-inflammatory cytokines, such as TNF-α and IL-6, which may be a consequence of JAK2/STAT3 and NF-κB pathway involvements. This study provides useful data for further exploration and application of boldine and reticuline as potential anti-inflammatory medicines.

HHX-5, a derivative of sesquiterpene from Chinese agarwood, suppresses innate and adaptive immunity via inhibiting STAT signaling pathways.

Induction of excessive, prolonged, or dysregulated immune responses causes immunological disorders, such as inflammatory diseases, autoimmune diseases, allergic diseases, and organ-graft rejections. In the present study, we investigated the inhibitory effects of HHX-5, a derivative of sesquiterpene from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat above immunological disorders. The results showed that HHX-5 significantly inhibited the activation of macrophages and neutrophils which play important roles in innate immunity. Furthermore, HHX-5 strongly suppressed adaptive immunity via inhibiting differentiation of naive CD4+ T cells into Th1, Th2, and Th17 cells and suppressing activation, proliferation and differentiation of CD8+ T cells and B cells. The mechanism study showed that HHX-5 significantly inhibited STAT1 signaling pathway in macrophages and suppressed STAT1, STAT4, STAT5, and STAT6 signaling pathways in naive CD4+ T cells. In conclusion, we demonstrated that HHX-5 can strongly inhibit innate and adaptive immunity via suppressing STAT signaling pathways and has potential to be developed into therapeutic drug for treat immunological disorders.

The Genus Neolitsea of Lauraceae: A Phytochemical and Biological Progress†

As one of the biggest genera in Lauraceae, Neolitsea owns a great application potential in industrial and traditional medical fields. Modern phytochemical and biological investigations revealed its structural diversity and diverse activities. This review summarizes the most recent progress on this regards, hopefully to provide a reference for full use and development of the Neolitsea resource.

Ilex asprella aqueous extracts exert in vivo anti-inflammatory effects by regulating the NF-κB, JAK2/STAT3, and MAPK signaling pathways

ETHNOPHARMACOLOGICAL RELEVANCE Ilex asprella (Hook. et Arn.) Champ. ex Benth. (IA) is a representative medicinal plant from the South of the Five Ridges of China. Its roots (RIA) and stems (SIA) have been traditionally used for the inflammation-related diseases, such as acute and chronic pharyngitis, cough, and sore throats. AIM OF THE STUDY To evaluate the in vivo anti-inflammatory effects of IA extracts to provide evidence for its traditional use and to enhance the knowledge of the medicinal properties of IA. MATERIALS AND METHODS Models of xylene-induced ear edema in mice and carrageenan-induced paw edema in rats were used for the pharmacological evaluations. The mice were randomly divided into eight groups (n = 10 per group): a model group, a positive control group [dexamethasone (Dex), 10 mg/kg, intragastrically (i.g.)], RIA aqueous extract groups with three dosages (30, 15, and 7.5 mg/kg, i.g.), and SIA aqueous extract groups with three dosages (60, 30, and 15 mg/kg, i.g.). The rats were randomly divided into eight groups (n = 6 per group): a model group, a positive control group [acetylsalicylic acid (ASA), 300 mg/kg, i.g.], RIA groups with three dosages (80, 40, and 20 mg/kg, i.g.) and SIA aqueous extract groups with three dosages (160, 80, and 40 mg/kg, i.g.). Histological examinations of the ear and paw tissues were observed by hematoxylin-eosin (HE) staining, and neutrophil elastase levels were assessed in ear tissues by immunohistochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured by ELISAs, and expression levels of TNF-α, IL-6, and IL-1β in rat paw tissues were measured by RT-PCR. The signal transduction proteins p65, IκBα, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), p38 mitogen-activated protein kinases (p38), extracellular regulated protein kinases (ERK1/2), and c-Jun N-terminal kinase (JNK) in the rat paw tissues were investigated by western blot analyses. RIA and SIA were characterized by HPLC and LC-MS analyses, and the components were confirmed by comparison with isolated compounds. RESULTS Intragastric administration with RIA (30 mg/kg) and SIA (60, 30 mg/kg) significantly mitigated ear edema in mice. RIA administration at 80 and 40 mg/kg reduced paw edema in rats 2‒3 h after injection. SIA administration with 160 mg/kg inhibited paw edema in rats after the injection of carrageenan for 1‒4 h, and SIA administration at 80 mg/kg inhibited paw edema after the injection of carrageenan for 2‒4 h. Meanwhile, RIA (80, 40 mg/kg) and SIA (160, 80 mg/kg) reduced inflammatory cell infiltration in the ear and paw tissues and infiltration of neutrophil leukocytes in rat paw tissues. RIA (80, 40, and 20 mg/kg) and SIA (160, 80, and 40 mg/kg) notably inhibited the increases of TNF-α, IL-6 and IL-1β in the serum and mRNA expression in the rat paw tissues. RIA (80, 40 mg/kg) and SIA (160, 80 mg/kg) reduced the p-p65/p-IκBα, p-JAK2/p-STAT3, and p-p38/p-ERK1/2/p-JNK levels in the pathological tissues of the animals. Phenolic acids and triterpenoids likely contributed to the anti-inflammatory activity. CONCLUSIONS Both RIA and SIA aqueous extracts showed anti-inflammatory effects in vivo in a dose-independent manner (20‒80 and 40‒160 mg/kg, respectively). The underlying mechanisms are mediated by inhibiting the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β via regulation of the NF-κB, JAK2/STAT3, and MAPK signaling pathways. The present results provided pharmacological evidence that stems are alternative medicinal parts of IA but function at different doses. Additionally, this study supports the use of IA as an anti-inflammatory herbal medicine.