Quinone-rich fraction of Ardisia crispa (Thunb.) A. DC roots alters angiogenic cascade in collagen-induced arthritis.

Rheumatoid arthritis (RA) is a chronic joint disorder, of which, excessive angiogenesis is the well-established factor contributing to synovitis and joint destruction. Ardisia crispa (Primulaceae) is a medicinal herb with evidenced anti-angiogenic properties, attributed to 2-methoxy-6-undecyl-1,4-benzoquinone (BQ) found in its roots. However, it is still unclear how BQ is able to inhibit angiogenesis in RA. Hence, we investigated the anti-arthritic potential of quinone-rich fraction (QRF) separated from Ardisia crispa roots hexane extract (ACRH) by targeting angiogenesis on collagen-induced arthritis (CIA) in rats. The QRF was priorly identified by quantifying the BQ content in the fraction using GC-MS. Male Sprague-Dawley rats (n = 6) were initially immunised with type II collagen (150 µg) subcutaneously at the base of the tail on day 0. QRF (3, 10, and 30 mg/kg/day) and celecoxib (5 mg/kg/day) were orally administered for 13 consecutive days starting from day 14 post-induction, except for the vehicle and arthritic controls. QRF at all dosages moderately ameliorated the arthritic scores, ankle swelling, and hind paw oedema with no significant (p > 0.05) modulation on the bodyweights and organ weights (i.e., liver, kidney, and spleen). Treatment with QRF at 3, 10, and 30 mg/kg, significantly (p < 0.05) attenuated VEGF-A, PI3K, AKT, NF-κB, p38, STAT3, and STAT5 proteins and markedly restored the increased synovial microvessel densities (MVD) to the normal level in arthritic rats in a dose-independent manner. In conclusion, QRF conferred the anti-arthritic effect via angiogenesis inhibition in vivo, credited to the BQ content and synergism, at least in part, by other phytoconstituents.

Cardiovascular risk prediction with cardio-ankle vascular index in the malaysian cohort study.

The cardio-ankle vascular index (CAVI) is an important parameter assessing arterial function. It reflects arterial stiffness from the origin of the aorta to the ankle, and the algorithm is blood pressure independent. Recent data have suggested that a high CAVI score can predict future cardiovascular disease (CVD) events; however, to date, no study has been done in Malaysia. We conducted a prospective study on 2,168 The Malaysian Cohort (TMC) CVD-free participants (971 men and 1,197 women; mean age 51.64 ± 8.38 years old) recruited from November 2011 to March 2012. This participants were followed-up until the emergence of CVD incidence and mortality (endpoint between May to September 2019; duration of 7.5 years). Eligible participants were assessed based on CAVI baseline measurement which categorised them into low (CAVI <9.0) and high (CAVI ≥ 9.0) scores. The CVD events in the group with high CAVI (6.5 %) were significantly higher than in the low CAVI (2.6 %) group (p < 0.05). CAVI with cut-off point ≥ 9.0 was a significant independent predictor for CVD event even after adjustment for male, ethnicity, age, and intermediate atherogenic index of plasma (AIP). Those who have higher CAVI have 78 % significantly higher risk of developing CVD compared to those with the low CAVI (adjusted OR [95 % CI] = 1.78 [1.04 - 3.05], p =0.035). In addition, the participants with higher CAVI have significantly lower survival probability than those who have lower CAVI values. Thus, this study indicated that the CAVI can predict CVD event independently among the TMC participants.

Bioactive fractions and compound of Ardisia crispa roots exhibit anti-arthritic properties mediated via angiogenesis inhibition in vitro.

BACKGROUND: Ardisia crispa (Thunb.) A.DC (Primulaceae), is a medicinal herb traditionally used by Asian people as remedies to cure inflammatory related diseases, including rheumatism. The plant roots possess various pharmacological activities including antipyretic, anti-inflammation and antitumor. Previous phytochemical studies of the plant roots have identified long chain alkyl-1,4-benzoquinones as major constituents, together with other phytochemicals. Hexane fraction of the plant roots (ACRH), was previously reported with anti-angiogenic and anti-arthritic properties, while its effect on their anti-arthritic in vitro, is yet unrevealed. Considering the significance of angiogenesis inhibition in developing new anti-arthritic agent, thus we investigated the anti-arthritic potential of Ardisia crispa roots by suppressing angiogenesis, in vitro. METHODS: Ardisia crispa roots hexane extract (ACRH) was prepared from the plant roots using absolute n-hexane. ACRH was fractionated into quinone-rich fraction (QRF) and further isolated to yield benzoquinonoid compound (BQ), respectively. In vitro experiments using VEGF-induced human umbilical vein endothelial cells (HUVECs) and IL-1ß-induced human fibroblast-like synoviocytes for rheumatoid arthritis (HFLS-RA) were performed to evaluate the effects of these samples on VEGF-induced HUVECs proliferation and tube formation, and towards IL-1ß-induced HFLS-RA proliferation, invasion, and apoptosis, respectively. Therapeutic concentrations (0.05, 0.5, and 5 µg/mL) tested in this study were predetermined based on the IC50 values obtained from the MTT assay. RESULTS: ACRH, QRF, and BQ exerted concentration-independent antiproliferative effects on VEGF-induced HUVECs and IL-1ß-induced HFLS-RA, with IC50 values at 1.09 ± 0.18, 3.85 ± 0.26, and 1.34 ± 0.16 µg/mL in HUVECs; and 3.60 ± 1.38, 4.47 ± 0.34, and 1.09 ± 0.09 µg/mL in HFLS-RA, respectively. Anti-angiogenic properties of these samples were verified via significant inhibition on VEGF-induced HUVECs tube formation, in a concentration-independent manner. The invasiveness of IL-1ß-induced HFLS-RA was also significantly inhibited in a concentration-independent manner by all samples. ACRH and BQ, but not QRF, significantly enhanced the apoptosis of IL-1ß-induced HFLS-RA elicited at their highest concentration (5 µg/mL) (P < 0.05). CONCLUSIONS: These findings highlight the bioactive fractions and compound from Ardisia crispa roots as potential anti-arthritic agents by inhibiting both HUVECs and HFLS-RA's cellular functions in vitro, possibly mediated via their anti-angiogenic effects.