Chlorogenic acid prevents ovariectomized-induced bone loss by facilitating osteoblast functions and suppressing osteoclast formation.

Osteoporosis is a usual bone disease in aging populations, principally in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are associated to a different of adverse effects. Du-Zhong is usually applied in Traditional Chinese Medicine to strengthen bone, regulate bone metabolism, and treat osteoporosis. Chlorogenic acid is a major polyphenol in Du-Zhong. In the current study, chlorogenic acid was found to enhance osteoblast proliferation and differentiation. Chlorogenic acid also inhibits the RANKL-induced osteoclastogenesis. Notably, ovariectomy significantly decreased bone volume and mechanical properties in the ovariectomized (OVX) rats. Administration of chlorogenic acid antagonized OVX-induced bone loss. Taken together, chlorogenic acid seems to be a hopeful molecule for the development of novel anti-osteoporosis treatment.

Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2-positive breast cancer.

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.

HPLC/ESI-MS and NMR Analysis of Chemical Constitutes in Bioactive Extract from the Root Nodule of Vaccinium emarginatum.

Vaccinium emarginatum Hayata is a medicinal plant that has been historically used in ethnopharmacy to treat diseases in Taiwan. The objective of this study is to evaluate the anti-cancer and anti-bacterial constitutes from the root nodule extract of V. emarginatum. The chemical composition of V. emarginatum fractions was analyzed by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and the chemical constitutes were isolated and structurally identified by nuclear magnetic resonance (NMR) spectroscopy. Bioassay-guided chromatography showed that the ethyl acetate (EA) fraction was bioactive on the hepatocellular carcinoma (HepG2). By LC-ESI-MS/MS analysis, twenty peaks of EA fraction were partially identified and the phytochemical investigation of the fractions led to the isolation and identification of protocatuchuic acid (1), epicatechin (2), catechin (3), procyanidin B3 (4), procyanidin A1 (5), hyperin (6), isoquercetin (7), quercetin (8), lupeol (9), beta-amyrin (10), and alpha-amyrin (11). Both procyanidin B3 and A1 exhibited anti-proliferative activity against HepG2 and gastric adenocarcinoma (AGS) cells at IC50 values between 38.4 and 41.1 µM and 79.4 and 83.8 µM, respectively. In addition, isoquercetin displayed the strongest anti-proliferative activity against the HepG2, lung carcinoma (A549), and AGS cell at 18.7, 24.6 and 68.5 µM, respectively. Among the triterpenoids, only lupeol showed the inhibitory activity against all tested tumor cell lines at IC50 values between 72.9 and 146.8 µM. Furthermore, procyanidins B3, A1 and isoquercetin displayed moderate anti-bacterial activity against Staphylococcus aureus. In conclusion, this study provides background information on the exploitation of V. emarginatum as a potential natural anti-cancer and anti-bacterial agent in pharmaceutical research.

Effects of Bilayer Nanofibrous Scaffolds Containing Curcumin/Lithospermi Radix Extract on Wound Healing in Streptozotocin-Induced Diabetic Rats.

Impaired growth factor production, angiogenic response, macrophage function, and collagen accumulation have been shown to delay wound healing. Delayed wound healing is a debilitating complication of diabetes that leads to significant morbidity. In this study, curcumin and Lithospermi radix (LR) extract, which are used in traditional Chinese herbal medicine, were added within nanofibrous membranes to improve wound healing in a streptozotocin (STZ)-induced diabetic rat model. Gelatin-based nanofibers, which were constructed with curcumin and LR extract at a flow rate of 0.1 mL/hour and an applied voltage of 20 kV, were electrospun onto chitosan scaffolds to produce bilayer nanofibrous scaffolds (GC/L/C). The wounds treated with GC/L/C exhibited a higher recovery rate and transforming growth factor-beta (TGF-ß) expression in Western blot assays. The decreased levels of pro-inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), provided evidence for the anti-inflammatory effects of GC/L/C treatment. Chronic wounds treated with GC/L/C achieved better performance with a 58 ± 7% increase in recovery rate on the seventh day. Based on its anti-inflammatory and wound-healing effects, the GC/L/C bilayer nanofibrous scaffolds can be potential materials for chronic wound treatment.

Effects of Different Concentrations of Collagenous Peptide from Fish Scales on Osteoblast Proliferation and Osteoclast Resorption.

The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.

Clinical effectiveness of acupuncture for carpal tunnel syndrome.

Acupuncture and electroacupuncture treatments of symptomatic carpal tunnel syndrome (CTS) may improve symptoms and aid nerve repair as well as improve sensory and motor functions. However, limited evidence is available regarding the effects of these treatments based on comprehensive evaluation methods. This research completed the treatment and evaluation of 26 patients with confirmed CTS. Participants were divided into two treatment groups based on a modified neurophysiological grading scale. Of the total number of participants, 15 received acupuncture and 11 received electroacupuncture on both upper limbs. Acupoints were PC-7 (Daling) and PC-6 (Neiguan) along the pericardial meridian compatible with the median nerve tract. The treatment program consisted of 24 sessions of 15 min duration over 6 weeks. After electroacupuncture treatments, symptom severity was evaluated using the short clinical questionnaire by Lo and Chiang, which indicated improvements in the respective symptom severity score. After the acupuncture treatment, grip strength in the major symptomatic side in CTS patients could be significantly increased. Electrophysiology evaluation likewise indicated a significant increase in the distal median motor amplitude of the palm-wrist segment. In addition, Tinel's sign significantly decreased in the major symptomatic side. Our findings indicated that electroacupuncture could improve symptomatology, while acupuncture could exert positive therapeutic effects for CTS patients, as evidenced by improved symptomatology, grip strength, electrophysiological function, and physical provocation sign.

Protective effect of Flos carthami extract against ethylene glycol-induced urolithiasis in rats.

Flos carthami (FC), also known as Carthamus tinctorius, is a traditional Chinese herbal plant that has been prescribed since centuries for treating various symptoms related to blood circulation improvement. This study aimed to investigate the effects of FC on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. A total of 50 male Sprague-Dawley rats were divided into the following 6 groups: group 1, as the normal control (n = 5); group 2 received gastric gavages of starch and 0.75% EG (placebo, n = 5) as a stone inducer; group 3 (n = 10) received EG and potassium citrate as positive controls; group 4 (n = 10) received 0.75% EG and 300 mg/day FC; group 5 (n = 10) was treated with EG and 600 mg/day FC; group 6 (n = 10) received with EG and 1,200 mg/day FC. For all experimental animals, 24-h urine and blood samples were analyzed at the beginning and end of the experiment. Kidney tissue was histopathologically examined using a polarized light microscope, and crystal deposits were evaluated by a semi-quantitative scoring method; these scores were significantly lower in the FC groups (600 and 1,200 mg/day) than in the placebo group. Thus, FC administration appeared to inhibit the deposition of CaOx crystal EG-fed rats. We, therefore, consider that FC may be effective for preventing stone disease, albeit with certain side effects, such as a bleeding tendency. Further clinical trials are needed for evaluating its benefits and possible side effects.

A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats.

We investigated the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline and final 24 h urine samples were collected individually; biochemical data of urine and serum were also obtained at the beginning and at the end of the experiment. After 4 weeks, animals were killed and kidneys were harvested. The kidney specimens were examined by polarized light microscopy and the crystal deposits were evaluated by a semi-quantitative scoring method using computer software (ImageScoring). The results revealed that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula.

Wu-Ling-San formula inhibits the crystallization of calcium oxalate in vitro.

Urinary stone disease is a common disease and has a high rate of recurrence. There is no ideal long-term medical treatment to prevent the recurrence of urinary stones. Wu-Ling-San (WLS) formula has been used for centuries in China for long-term treatment of urological diseases. However, no pharmacological studies have been conducted to evaluate its effect on urinary stone disease. Therefore, using a photospectrometer, we studied the effects of WLS on nucleation, growth and aggregation of calcium oxalate in vitro. The results showed that WLS extract significantly slowed the speed of calcium oxalate (CaOx) crystal nucleation. WLS extracts at concentrations of 6.25, 12.5, 25, and 50 mg/ml inhibited nucleation of calcium oxalate crystallization by 344, 387, 543, and 943%, respectively. WLS extracts did not inhibit the growth of CaOx crystallization; however, WLS extracts at concentrations of 12.5 and 25 mg/ml significantly inhibited the aggregation of CaOx crystallization by 74.24% and 75.05%, respectively. WLS extract at a concentration of 50 mg/ml inhibited CaOx aggregation by 92.49%. In conclusion, our results indicate that WLS extract inhibited calcium oxalate nucleation and aggregation, and may have the potential to prevent stone recurrence.