Rubus Coreanus Miquel Extract Research Articles

Augmented Antitumor Effect of Unripe Rubus coreanus Miquel Combined with Oxaliplatin in a Humanized PD-1/PD-L1 Knock-In Colorectal Cancer Mouse Model.

Immune checkpoint inhibitors (ICIs) have been shown to be extraordinarily effective in patients with colorectal cancer (CRC). However, the current ICIs still have adverse effects and limited efficacy of ICI monotherapy. We used a natural product to overcome the vulnerability of ICIs and tried a combination therapy with oxaliplatin to enhance the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) blockade anticancer effect. In the present study, we evaluated the T cell-mediated antitumor immunity with Unripe Rubus coreanus Miquel extract (RCE), which exerts anticancer properties via PD-1/PD-L1 blockade, combined with oxaliplatin in a co-culture cell model and allograft tumor humanized PD-1 mice. We found that RCE plus oxaliplatin apparently activates hPD-1 tumor-infiltrating CD8+ T cells, resulting in elevations of released interleukin-2 (IL-2) and granzyme B (GrB), and kills hPD-L1 MC38 CRC cells. RCE plus oxaliplatin considerably reduced tumor growth in humanized PD-1/PD-L1-expressing mouse MC38 CRC allograft. Moreover, RCE plus oxaliplatin remarkably increased the infiltration of CD8+ T cells in tumor tissues, as well as increasingly produced GrB of tumor-infiltrating CD8+ T cells in the tumor microenvironment. Our study delineated combination therapy with RCE as a PD-1/PD-L1 blockade and oxaliplatin to improve the response to immune checkpoint blockade therapy in conjunction with standard chemotherapy regimens in CRC.

Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Promotes Lipolysis and Thermogenesis In Vitro and In Vivo.

Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.

Effects of Rubus coreanus Miquel extracts on the proliferation and differentiation of mouse osteoblast-like MC3T3-E1 cells

Rubus coreanus Miquel (RCM), one a type of edible red raspberry, grows wild in Korea and China and its unripe fruit has been used as a folk medicine for the treatment of impotence and as a diuretic agent. The goal of this study was to investigate the effects of RCM on the proliferation and differentiation of mouse osteoblast-like MC3T3-E1 cells. In this study, RCM extract (1-10 μg/mL) enhanced the viability of osteoblast cell. RCM extract also increased alkaline phosphatase (ALP) activity and osteocalcin secretion of MC3T3-E1 cells (significant at 1-10 μg/mL). Especially, at a concentration of 10 μg/mL ALP activity was increased by approximately 4.3 times in comparison with the control. Alizarin red staining and osteocalcin secretion assay showed that RCM extract stimulates differentiation of osteoblast cells by inducing the activation of mineralization. Moreover, reverse transcriptase polymerase chain reaction and western blotting assay indicated that RCM extract induced the differentiation at mRNA and protein level. These results suggest that RCM extract enhanced the osteoblast function by increasing the proliferation and differentiation of osteoblast like MC3T3-E1 cells.

Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Regulates AMPK, SREBP-2, HMGCR, and INSIG-1 Signaling and Cholesterol Metabolism In Vitro and In Vivo

Our previous study demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5-uRCK and one of its major bioactive compounds, ellagic acid, decrease cellular and plasma cholesterol levels. Thus, we investigated the hypocholesterolemic activity and mechanism of 5-uRCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5-uRCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5-uRCK extract and ellagic acid, which also caused histological improvements. The MDA content in the aorta and serum was significantly decreased after oral administration of 5-uRCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5-uRCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5-uRCK and ellagic acid suppressed the nuclear translocation and activation of SREBP-2, which is a key transcription factor in cholesterol biosynthesis. In conclusion, our results suggest that 5-uRCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol.

A protective and antioxidant and whitening effect of B16F10 melanoma cell induced by ultraviolet A by Rubus coreanus Miquel extract

A protective and antioxidant and whitening effect of B16F10 melanoma cell induced by ultraviolet A by Rubus coreanus Miquel extract

Chemical Characterization and Insecticidal Activity of Rubus coreanus Miquel Extracts (Leaves, Fruits and Stems) against Three Agricultural Insect Pests, Myzus persicae, Plutella xylostella and Spodoptera litura

Chemical Characterization and Insecticidal Activity of Rubus coreanus Miquel Extracts (Leaves, Fruits and Stems) against Three Agricultural Insect Pests, Myzus persicae, Plutella xylostella and Spodoptera litura

Rubuscoreanus Miquel extract causes apoptosis of doxorubicin-resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation.

Cancer cells can acquire an anticancer, drug-resistant phenotype following chemotherapy, which is tightly linked to cancer malignancy and patient survival rates. Therefore, the identification of options to treat chemotherapy‑resistant cancer cells is an urgent requirement. Rubuscoreanus Miquel (RCM) has long been used as a source of food. In addition, it has been reported that RCM has effective functions against particular diseases, including cancer and inflammation. In the present study, it was demonstrated that RCM extract caused the apoptotic cell death of doxorubicin‑resistant NCI/ADR‑RES ovarian cancer cells by phosphorylating c‑Jun N‑terminal kinase (JNK). The RCM‑mediated reduction of cell viability showed no synergism with doxorubicin. In addition, ellagic acid and quercetin, which are phytochemicals found in RCM, also caused apoptosis of the NCI/ADR‑RES cells. In subsequent investigations of the RCM‑altered signaling pathway, RCM extract, ellagic acid and quercetin were found to commonly induce the phosphorylation of JNK and AKT. Additionally, the inhibition of JNK with SP600125 repressed the apoptotic cell death induced by RCM extract, ellagic acid and quercetin, and the inhibition of JNK appeared to switch apoptosis to necrosis. JNK inhibition also reduced the phosphorylation of AKT, which was induced by RCM extract, ellagic acid and quercetin, suggesting that the phosphorylation of JNK is required for AKT phosphorylation in RCM‑, ellagic acid‑ or quercetin‑induced apoptotic cell death. Therefore, the data obtained in the present study led to the conclusion that RCM caused apoptosis of doxorubicin‑resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation, and suggested that RCM may be effective in the treatment of chemotherapy‑resistant cancer cells.

복분자 추출물을 포함하는 김치 두루치기의 저온 저장 특성

본 연구는 열수 추출된 복분자 분말을 김치두루치기에 첨가한 후 저온저장에 따른 품질 안정성을 평가하기 위해 수행되었다. 복분자 추출물의 DPPH와 수퍼옥사이드 라디칼 소거 활성은 70.63%와 57.87%로 각각 비교적 높게 나타났다. 샘플은 대조구(무처리), T1 (15% 복분자 추출물), T2 (30 복분자 추출물), T3 (0.5% 아스코르빅산; 양성대조구)를 첨가하여 제조하였다. 복분자 추출물 첨가 샘플은 대조구와 양성 대조구에 비교하여 저장 기간에 따라 pH는 온화하게 변화되는 것으로 나타났고, 대조구에 비교하여 보수력이 개선되었다. 육색은 대부분 시간 경과가 될수록 증가되는 경향성을 보였으며, 대조구보다 더 낮은 변화의 폭을 보였다. 지질 과산화는 저장일수와 처리에 상관없이 거의 변화가 없는 것으로 나타났으며, 단백질 변패도는 대조구에 비교하여 낮은 것으로 나타났다. 관능분석 결과 T1과 T2는 대조구와 양성대조구에 비교하여 더 좋은 맛과 풍미를 가지며, 전체 기호도가 더 좋은 것으로 나타났다. 따라서 복분자 첨가 김치 두루치기는 제품의 저장 안정성을 개선하고, 제품의 기호도를 개선하는 것이 가능한 것으로 제의된다. The goal of this study was done for evaluating stability according to low-temperature storage of kimchi duruchigi supplemented with a hot water extract of Rubus coreanus Miquel (RCM). Total polyphenol and flavonoid contents in the RCM extract prepared from the hot water were detected by 293.34 μg CA/mg and 90.57 μg quecetin/mg, respectively. DPPH and superoxide radical scavenging activities of the extract were showed by relatively high values of 70.63 and 57.87%, respectively. Kimchi duruchigi was designed by control (non-treated), T1 (3% RCM extract), T2 (6% RCM extract), and T3 (0.1% ascorbic acid, a positive control). When compared with control and T3 groups, pHs of T1 and T2 groups supplemented with the RCM extract were gently changed depending on the storage time, and water holding capacities of T1 and T2 groups were improved in comparison with control group. Although meat color showed a tendency to most of increase according to the elapsed time, T1 and T2 groups showed less changes than that of control group. Lipid peroxidation appeared in a little bit changes regardless of the processing and storage days, but protein spoilages in T1 and T2 groups were found by lower changes when compared with the control group. As the results of sensory evaluation, T1 and T2 groups during storage had the better taste, flavor and acceptability than those of control and T3 groups. Therefore, we suggest that kimchi duruchigi supplemented with the RCM extract is a possible of improving the storage stability and product preference.

Review on Anti-Cancer and Anti-Imflammatory Activity from Rubus coreanus Miquel

In accordance to the increasing number of death due to cancer and side effects of chemotherapy, attention has recently focused on combined treatment of natural component and anti-tumor agent. Therefore development of safe and effective functional substances derived from natural materials is required. The emergence of various functional activities of Rubus coreanus Miquel, such as antioxidant, anticancer, anti-inflammatory, etc. is continuously increasing its consumption. To utilize the above activities, many products developed by using Rubus coreanus Miquel extracts in the areas of foods, liquors, and cosmetics and medicines. In this review, anti-cancer, anti-inflammatory activity and patents of Rubus coreanus Miquel are summarized. Further studies are needed to search for development of functional material from natural origin and various application possibility using stem, leaf and fruit of Rubus coreanus Miquel.

Anti-Obesity Effects on Unripe Rubus coreanus Miquel Extract in High Fat Diet-Induced Obese Mice

Aims: The objective of the present study was to evaluate the anti-obesity effects of unripe Rubus coreanus Miquel (uRC) in 3T3-L1 adipocytes and body weight, epididymal fat and perirenal fat weight, and lipid profiles in diet-induced obese (DIO) C57BL/6 mice. Methodology: The lipid accumulation in 3T3-L1 adipocytes was carried out Oil Red O staining. And uRC (50 and 100 mg/kg/day) were orally administered for 90 days from the day of feeding with high fat diet (HFD). The serum total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL)-cholesterol and low density lipoprotein(LDL)-cholesterol and glucose levels were measured using Alere cholesterol LDX system. And the serum glutamic oxaloacetic transaminase (GOT), Short Communication Jung et al; IJBcRR, 5(1): 20-26, 2015; Article no. IJBcRR.2015.003 21 glutamic pyruvic transaminase (GPT), blood urea nitrogen(BUN) and creatinine levels were measured using the respective kits. Results: Our results indicated that treatment with uRC dose-dependently inhibited lipid accumulation in 3T3-L1 adipocytes. Moreover, after oral administration for 12 weeks, uRC (50 and 100mg/kg/day) extract produced a significant decrease in the serum total cholesterol (TC), lowdensity lipoprotein (LDL) cholesterol, glucose and glutamic-oxaloacetic transaminase (GOT) levels of HFD-induced obese mice. Similarly, uRC extract elevated serum high density lipoprotein (HDL) cholesterol. These results suggest that uRC extract may be a useful resource for the management of obesity. Conclusion: These results suggest that uRC extract may be a useful resource for the management of obesity.

Rubus coreanus Miquel Inhibits Acetylcholinesterase Activity and Prevents Cognitive Impairment in a Mouse Model of Dementia

To find acetylcholinesterase (AChE) inhibitors for the prevention of neurological disorders, such as Alzheimer's disease, ethanol extracts of promising traditional edible Korean plants were tested. Among them, Rubus coreanus Miquel extract exhibited the most significant AChE inhibitory activity. The effect of R. coreanus extract on trimethyltin-induced memory impairment in mice was investigated using Y-maze and passive avoidance tests. Our results showed that administration of R. coreanus extract significantly improved alternation behavior and step-through latency. In addition, R. coreanus extract was sequentially fractionated, and the purified constituent was determined to be 3,4,5-trihydroxybenzoic acid.

Chemopreventive Effects ofRubus coreanusMiquel on Prostate Cancer

The growing incidence of prostate cancer and the traditional use of Rubus coreanus Miquel (RCM) for prostate health led us to compare RCM extracts and to test their efficacy in inhibiting the growth of prostate cancer cells differing in androgen dependency. Ethanol extracts of unripe RCM (EUR) were more effective in reducing cell viability than water extracts or ripe RCM. EUR-induced growth inhibition, as indicated by significant reductions in numbers of proliferating cells and decreases in the protein levels of proliferating cell nuclear antigen (PCNA), cyclin D1 and CDK4, was greater in the androgen-dependent LNCaP cells than in the androgen-independent DU145 cells. EUR also induced mitochondrial-mediated apoptosis in prostate cancer cells by reducing Bcl-2 and Bcl-(X)L levels, but increased Bax levels. Nevertheless, the LNCaP cells were more sensitive to EUR-induced apoptosis and displayed sub-G1 and late apoptotic cell populations, whereas the DU145 cells did not. Our findings suggest that EUR suppresses the growth of prostate cancer cells by anti-proliferative and/or pro-apoptotic effects, and that these effects are stronger in androgen-dependent cells.

Rubus coreanus Miquel inhibits prostate cancer invasion and migration by reduction of MMP‐2 and MMP‐9 expression

The growing incidence of prostate cancer and the traditional use of Rubus coreanus Miquel (RCM) for prostate health led us to compare RCM extracts and to test their efficacy in inhibiting the metastasis of prostate cancer cells. DU145 and PC‐3 cells were treated with unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), or ripe RCM water extract (RH) at concentration of 100 μg/ml for 24 h then matrix metalloproteinase‐2 (MMP‐2), MMP‐9, membrane type 1‐MMP (MT1‐MMP), MT2‐MMP, tissue inhibitors of metalloproteinase‐1 (TIMP‐1), and TIMP‐2 expressions were assessed by western blot and real‐time polymerase chain reaction (PCR). Invasion and wound healing assays were also performed. UE and UH treatment significantly reduced wound healing in a dose‐dependent manner. Furthermore, UE and UH treatment decreased MMP‐2 and ‐9 mRNA and protein expressions but increased TIMP‐1 and TIMP‐2 mRNA and protein expressions. These results suggest that unripe RCM inhibits migration and invasion of prostate cancer cells by reducing MMPs and inducing TIMPs expression. This research was supported financially by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Project No. 2009‐0068227)

복분자를 첨가한 젤리의 품질특성

복분자 젤리의 최적 레시피를 개발하고자 복분자 추출액, 복분자 향, 설탕, 물엿의 함량을 달리한 시료를 제조하여 일반성분, texture, 색도, 관능평가 등과 같은 품질특성에 대하여 살펴보았다. 일반성분은 수분이 19.0%, 조단백질이 0.8%이었으며, 조지방 및 조회분은 검출되지 않았다. 복분자 젤리의 texture는 복분자 추출액 양이 적은 제품이 복분자 추출액 양이 많은 제품보다 경도, 검성, 탄력성, 응집성 및 씹힘성이 유의적으로 높게 나타났다. L값은 복분자 추출액의 양이 적은 제품과 설탕 함량이 많은 제품이 복분자 추출액의 첨가량이 많은 제품과 설탕 첨가량이 적은 제품에 비하여 높게 나타났고, b값은 복분자 추출액 또는 설탕의 첨가량이 많은 제품이 적은 제품보다 높게 나타났다. 관능평가 항목중 향미, 색도, 당도, 경도(씹는 느낌), 끈적임, 전체적인 기호도를 모두 충족시키는 최적의 레시피는 물 240 g, 설탕 120 g, 물엿 110 g, 한천 4 g, 복분자 추출액 20 g, 복분자 향 0.3 g으로 제조하는 B 제품으로 사료된다.

복분자 추출물의 항산화활성 및 인간 위암 세포주에 대한 유전적 손상 유도

본 연구에서는 다양한 기능성을 가지는 복분자를 80% methanol로 추출한 후 분획물들을 제조하여 항산화 효과 및 인간 유래 위암세포인 AGS와 KatoIII을 이용하여 성장 저해 효과와 DNA손상을 측정하였다. 항산화 효과를 측정해 보기 위하여 총 폴리페놀 함량과 플라보노이드 함량, DPPH free radical의 소거활성을 측정하였는데, 먼저 폴리페놀의 경우 butanol fr., ethylacetate fr., water fr.순으로 나타났고 특히 butanol fr.의 경우 <TEX>$546.25{\mu}g/mg$</TEX>의 매우 높은 폴리페놀 함량을 확인 할 수 있었다. 플라보노이드의 함량 결과 ethylacetate fr., butanol fr., water fr.,순으로 나타났으며 ethylacetate fr.의 경우 <TEX>$141.78{\mu}g/mg$</TEX>의 높은 플라보노이드 함량을 확인할 수 있었다. DPPH free radical의 소거활성에서는 폴리페놀 함량의 순서와 같은 효과를 보였으며, 합성 항산화제인 BHA의 <TEX>$RC_{50}$</TEX>값 <TEX>$3{\mu}g/ml$</TEX>보다 water fr.을 제외하고 더 좋은 소거능을 확인 할 수 있었다. 인간 유래 위암세포주의 성장 저해 효과를 살펴본 결과 AGS와 KatoIII 세포주 모두 butanol fr.에서 가장 좋은 저해능을 나타내었고, butanol fr., ethylacetate fr., water fr. 순서로 저해효과를 나타내었다. DNA손상을 측정한 결과 역시 이와 같은 순으로 나타났으며, butanol fr.에서 1시간 이내에 약 50%정도의 손상유도 효과를 보였다. 이상의 결과에서 복분자 methanol추출물과 각각의 분획물은 항산화 효과 및 위암 세포주에 대한 성장 저해 활성 및 높은 DNA손상 유도 효과를 갖고 있음을 알 수 있었다. Rubus coreanus Miquel (RCM), a type of red raspberry, grows wild in Korea and China and its unripe fruit is used as a folk medicine for the treatment of impotence and as a diuretic. RCM was extracted with methanol and then further fractionated it into for different types. In this study, we investigated the antioxidant activity of a RCM extract (ext.) and its fraction (fr.). DPPH free radical scavenging activity assay, total polyphenols contents, total flavonoids contents assay were used to analyze antioxidant activity. The DPPH free radical scavenging activity <TEX>$(RC_{50}:1.67{\mu}g/ml)$</TEX> and total polyphenols contents <TEX>$(546.25{\mu}g/mg)$</TEX> were higher in butanol fraction than in other fr. And total flavonoids contents was higher in ethylacetate fr. <TEX>$(141.78{\mu}g/mg)$</TEX>. We applied comet assay to measure the DNA damage in the individual cells and exposed time course at <TEX>$IC_{50}$</TEX>. Comet assay is a rapid and sensitive fluorescent microscopic method to examine DNA damage and repair at individual cell level. The butanol fro from RCM significantly induced 54.12%, 57.95% of DNA damage after treated RCM for 8 hr. In conclus

복분자(Rubus coreanus Miquel) 추출물이 MC3T3-E1 조골세포의 활성과 분화에 미치는 영향

The osteoblastic cell activity is important for born formation, thus, this study was performed to investigation of that the effect of edible sources, Rubus coreanus Miquel (RCM), on the proliferation and differentiation of MC3T3-E1 osteoblastic like cell. The effects of RCM extract on cell proliferation were measured by MTT assay. At 1, 10 μg/mL of RCM extract treated, that were elevated of cell proliferation to 103 and 142% via control, respectively. And the cell differentiation were measured as alkaline phosphatase (ALP) activity at 3, 9, 18, and 27 days. As the results, the 10 μg/mL was increased ALP activity more than 2.6 times compared with control, 1.4 times via positive control at 27th day (p<0.05). The optical concentration of RC extract was rechecked by ALP staining and Alizarin Red staining for investigation of the induction of ALP activity, nodule formation by mineralization. mRNA expression analysis showed that the RCM (10μg/mL) increased in SOX9 as well as ALP in MC3T3-E1 cells. These results suggest that RC extract was stimulates the MC3T3-E1 cell proliferation and differentiation.