Lycii Radicis Research Articles

The effect of Lycii Radicis Cortex extract on bone formation in vitro and in vivo.

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis.

Immunomodulatory Effects of Lycii Radicis Cortex Water Extract on Lipopolysaccharide-Activated RAW 264.7 Mouse Macrophages

The root bark of Lycium chinense Miller (Solanaceae), also known as Lycii radicis cortex, is one of famous plant-originated drugs in Korean medicine owing to its anti-tussive, anti-asthmatic, and antipyretic properties. In this study, the effect of Lycii radicis cortex water extract (LRC; 10 - 200μg/mL) on inflammatory mediators from lipopolysaccharide (LPS)-activated RAW 264.7 mouse macrophages was inspected. After 24 h incubation with LRC, cell viability, nitric oxide (NO), and various cytokines from RAW 264.7 were measured. LRC increased the cell viability of RAW 264.7 at concentrations of up to 200 μg/mL. LRC significantly inhibited the production of NO, granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-α (TNF-α), platelet derived growth factor-BB (PDGF-BB), interleukin (IL)-2, and IL-10 in LPS-activated RAW 264.7 (P < 0.05). As well, LRC diminished the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide-induced CXC chemokine (LIX). The current results suggest that LRC has immunomodulatory property to alleviate excessive immune reactions during the activation of macrophages by LPS.

Activity-guided isolation of NF-κB inhibitors and PPARγ agonists from the root bark of Lycium chinense Miller

Ethnopharmacological relevanceThe root bark of Lycium chinense Miller, Lycii Radicis Cortex, has been used in traditional Chinese medicine (TCM) to treat different inflammation-related symptoms, such as diabetes mellitus. The pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammation, while the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key modulator of genes involved in diabetes development. To identify putative active compound(s) from Lycii Radicis Cortex inhibiting NF-κB or activating PPARγ. Material and methodsUsing activity-guided fractionation, six extracts with different polarity, isolated fractions, and purified compounds from Lycii Radicis Cortex were tested for NF-κB inhibition and PPARγ activation in vitro. The structure of the purified compounds was elucidated by NMR and MS techniques. ResultsThe ethyl acetate extract and the methanol extract of Lycii Radicis Cortex suppressed tumor necrosis factor alpha (TNF-α)-induced activation of NF-κB, while the dichloromethane extract activated PPARγ. Nine phenolic amide analogues, including trans-N-(p-coumaroyl)tyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), dihydro-N-caffeoyltyramine (4), three neolignanamides (5–7), and two lignanamide (8, 9), were isolated and their inhibitory potential on NF-κB was determined (1–4 were also contained in water decoction). Two of the nine isolated phenolic amides inhibited TNF-α-induced NF-κB activation. Trans-N-caffeoyltyramine was verified as the key component responsible for the NF-κB inhibition with an IC50 of 18.4μM in our cell-based test system. Activation of PPARγ was attributed to a palmitic-acid enriched fraction which displayed concentration-dependent effect ablated upon co-treatment with the PPARγ antagonist T0070907. ConclusionsPhenolic amides were confirmed as main components from Lycii Radicis Cortex responsible for NF-κB inhibition. Fatty acids were identified as the major plant constituent responsible for the PPARγ activation. Structure-activity relationship analysis suggests that the NF-κB inhibitory activity of trans-N-caffeoyltyramine may be attributed to its Michael acceptor-type structure (α,β-unsaturated carbonyl group). The data of this study contribute to a better understanding of the molecular mechanism of action of Lycii Radicis Cortex extracts in the context of inflammation.

Anti-inflammatory effect of Lycii radicis in LPS-stimulated RAW 264.7 macrophages.

The root bark of Lycium barbarum (Lycii radicis cortex, LRC) is used as a cooling agent for fever and night sweats in East Asian traditional medicine. The inhibitory effect of LRC water extract on inflammation is unknown. In this study, the anti-inflammatory effect of LRC was investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage, RAW 264.7 cells. LRC extract significantly decreased the LPS-induced production of inflammatory mediators, nitric oxide (NO), prostaglandin (PG) E2 and pro-inflammatory cytokines, interleukin (IL)-1β and IL-6 in the cells. In addition, LRC extract inhibited the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA and protein, and inflammatory cytokines mRNA in the cells. The action mechanism of LRC underlies the blocking of LPS-mediated p38 and Jun N-terminal kinase (JNK), mitogen-activated protein kinases (MAPKs), and the nuclear factor (NF)-κB signaling pathway. These results indicate that LRC extract inhibits the inflammatory response in activated macrophages by down-regulating the transcription levels of inflammatory mediators and blocking the MAPKs and NF-κB pathway.

지골피, 산수유의 streptozotocin 유발 당뇨흰쥐에서의 효과 비교 연구

Objectives : This study aimed to compare the anti-diabetic efficacy of Lycii Radicis Cortex (Lycium chinense Mill.) and Corni Fructus (Cornus officinalis) on streptozotocin (STZ)-induced diabetes in rats. Methods : Male Sprague-Dawley rats were divided into four groups; normal, STZ-control, Lycii Radicis Cortex extract-administrated group (LRC) and Corni Fructus extract-administrated group(CF). Diabetes in rats was induced by intraperitonal injection with streptozotocin (STZ) a t doses of, 30 ㎎/㎏ (body weight) for 5 days (once per a day). STZ-induced diabetic rats were orally administrated LRC and CF extract daily for 4 weeks at doses of 300 ㎎/㎏. Fasting blood glucose, total cholesterol (TC) , triglyceride (TG), blood urea nitrogen (BUN) and creatinine were measured in sera of rats. Histopathologica l changes of kidney, liver and lung tissues were observed by microscope after H&E staining. Results : There were no differences in body and kidney weights, food intake and water intake in LRC- and CF-administrated groups compared with STZ control group. Howeve r, glucose, TC and TG levels in serum were significantly decreased in LRC-administrated groups compared with STZ-control group. In histopathological analysis of kidney, liver and lung, both LRC- and CF-administrated groups showed the inhibition of morphological damage. Conclusions : These results suggest that LRC and CF have a biological action on STZ-induced diabetes in rats via decreasing the serum TG and TG levels and may protect the m orphological changes of kidney, liver and lung.

Streptozotocin으로 유도된 당뇨 흰쥐에서 하소에 사용되는 한약의 항당뇨 효과 비교 연구

Objectives : To prove the channel-tropism theory in herbology, we investigated the anti-diabetic effect of six herbal plants used for lower wasting-thirst in streptozotocin-induced diabetic rats. Methods : Diabetes was induced in male Sprague-Dawley rats by consecutive injection of streptozotocin (30 mg/kg i.p.) for 5 days. The rats were divided into normal control, diabetic control, and diabetic treatment with Lycii Radicis Cortex (LRC, 300 mg/kg); Corni Fructus (CF, 300 mg/kg); Bombyx Batryticatus (BB, 50 mg/kg); Lycii Fructus (LF, 300 mg/kg); Phellodendri Cortex (PC, 300 mg/kg); Epimedii Herba (EH, 300 mg/kg); and glibenclimide (10 mg/kg) as a reference drug. Herbal extracts or reference drug were administered orally for 28 days. The changes of body weight, food intake and water intake, and serological markers such as blood glucose, serum total cholesterol, triglyceride (TG), blood urea nitrogen (BUN), and creatinine (Cr) were measured. Results : The decrease of body weight and the increase of food and water intake in STZ-induced diabetic rats was improved by the administration of CF and LF. Also, the enhancement of blood glucose and serum total cholesterol, TG, BUN and Cr in STZ-induced diabetic rats was significantly inhibited by the administration of CF, BB, LF and glibenclimide. On the other hand, EH strongly inhibited the increase of BUN and Cr in the sera of STZ-induced diabetic rats. Conclusions : These results suggest that among six herbal medicines used lower emaciation of emaciation-thirst disease, CF, BB, LF and EH show a characteristics including the channel-tropism theory.

Antidepressant-Like Effects of Lycii Radicis Cortex and Betaine in the Forced Swimming Test in Rats

The purpose of the present study was to examine the effect of Lycii Radicis Cortex (LRC) and betaine (BT) on immobility and neurochemical change in the forced swimming test (FST) in the rat. LRC, BT or fluoxentine was administered intraperitoneally to Sprague-Dawley rats three times (1, 5 and 23.5 h) before the FST. To investigate antidepressant-like effect, serotonin (5-HT) and norepinephrine (NE) were examined in the hippocampus and hypothalamus of rats. LRC (100 mg/kg) and BT (30, 100 mg/kg) significantly decreased the immobility time in the FST. LRC (100 mg/kg) significantly increased both 5-HT and NE levels in the hypothalamus of rats exposed to FST. BT (100 mg/kg) significantly increased 5-HT levels in the hypothalamus and hippocampus of rats. Taken together, these results demonstrated that improvement in the behavioral changes after LRC and BT administration may be mediated by elevation of 5-HT level in the hypothalamus and hippocampus, indicating a possible antidepressant-like activity. The present results suggest that the efficacy of LRC and BT in an animal model of depression may provide anti-depressant effects in human, which remains to be determined.

Lycii cortex radicis extract inhibits glioma tumor growth in vitro and in vivo through downregulation of the Akt/ERK pathway

Lycii cortex radicis (LCR) is a traditional Korean medicinal herb. The present study was undertaken to examine the effect of an LCR extract on glioma cell growth and to determine its molecular mechanism in U87MG human glioma cells. The LCR extract resulted in apoptotic cell death in a dose- and time-dependent manner. The LCR extract-induced cell death was associated with generation of reactive oxygen species (ROS). Western blot analysis showed that the LCR extract caused downregulation of Akt and ERK. The LCR-induced cell death was prevented by transfection with the constitutively active forms of Akt and MEK. Oral administration of LCR extracts in subcutaneous U87MG xenograft models reduced glioma tumor volume. Taken together, these findings suggest that the LCR extract results in human glioma cell death through mechanisms involving ROS generation, downregulation of Akt and ERK, and caspase activation invitro and reduces glioma tumor growth invivo. These data suggest that the LCR extract may serve as a potential therapeutic agent for malignant human glioblastomas.

Effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on Corticotropin-Releasing Factor, c-Fos, and Tyrosine Hydroxylase in Forced Swimming Test

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p

Evaluation of Samjunghwan, a traditional medicine, for neuroprotection against damage by amyloid-beta in rat cortical neurons

Aim of the study Samjunghwan (SJH) is a multi-herbal traditional medicine composed of Mori Fructus, Lycii Radicis Cortex, and Atractylodis Rhizoma Alba and it is clinically applied as an anti-aging agent in neurodegenerative disorders, to promote longevity. In the present study, we evaluated the neuroprotective effect of SJH in Alzheimer's disease induced by amyloid-beta (Abeta) and examined the related pathways. Materials and methods To evaluate the protective effect of SJH, we conducted thiazolyl blue tetrazolium bromide, lactate dehydrogenase, and MAP-2 staining assays of primary cultured rat cortical neurons stressed by Abeta 25–35. To investigate the possible mechanism of action, we examined the Bcl-2/Bax expression ratio, mitochondrial membrane potential (Δ ψ M ), cytochrome C release, and caspase-3 activation, focusing on the mitochondria-mediated apoptotic pathways. Results SJH at concentrations of 10 and 100 μg/ml provided significant protection of rat cortical neurons from Abeta 25–35 neurotoxicity. At the maximum effective dose of 100 μg/ml, SJH significantly increased the anti-apoptotic protein (Bcl-2)/pro-apoptotic protein (Bax) ratio and inhibited Δ ψ M depolarization, cytosolic cytochrome C release, and caspase-3 activation. Conclusion SJH appears to provide neuroprotection against mitochondria-mediated apoptotic pathways in this Abeta 25–35-induced Alzheimer's disease model.

Effects of Mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex on the Change of HPA-Axis and Catecholamic System in the Forced Swimming Test

ABSTRACT Objectives：In this study the antidepressant effects of mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex on the change of HPA-Axis and Catecholamic system was investigatedMethods：The forced swimming test(FST) was performed. The expression of corticotropin-releasing factor(CRF), c-Fos in the paraventricular nucleus(PVN), and tyrosine hydroxylase(TH) in the ventral tegmental area(VTA) and locus coeruleus(LC) was measured with immunohistochemical method and the concentration of seum adrenocorticotropic hormone(ACTH) was measured with ELISA method. And the experimental groups were divided into the extraction after mixing(A) and mixture after extraction(B). The effects of both group were compared. Results：The duration of immobility in the forced swimming test was significantly decreased in the A400 group(P<0.01). The expression of CRF in PVN were significantly reduced in the A100, A400, B100, B400groups(P<0.001). but the expression of c-fos in PVN weren't reduced in all groups. And the concentration of ACTH in Plasma were significantly reduced in the A 100 group(P<0.01). The expression of TH in LC were significantly reduced in the A 400, B 100 and B400 groups(P<0.05~P<0.01). Conclusion：Mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex has antidepressant effects. But the difference between mixing and extracting methods was not shown.Key words：Mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex, FST, HPA Axis system, Catecholaminergic system, antidepressant.

Goji (Lycium barbarumandL. chinense): Phytochemistry, Pharmacology and Safety in the Perspective of Traditional Uses and Recent Popularity

Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinense with consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as " Lycium barbarum polysaccharides", which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.

Cortex Lycii Radicis extracts improve insulin resistance and lipid metabolism in obese‐diabetic rats

Here we evaluate the effects of ethanol and aqueous extracts from Cortex Lycii Radicis (CLR) on insulin resistance and lipid metabolism in obese-diabetic rats, which were induced by high fat feeding for 3 weeks after injection with streptozotocin (STZ). Diabetic rats treated with ethanol or aqueous extracts of CLR at 15 and 30 g/kg dosage for 7 weeks, had decreased body weights, concentration of serum glucose, triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), while the insulin-sensitivity index (ISI) improved significantly compared with the control group. In addition, high contents of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and low adiponectin level were observed in the control group and levels of TNF-alpha and IL-6 in CLR groups showed obvious differences with the control group. Histopathologic examination also showed degrees of hepatocyte edema although hepatocyte ballooning degeneration was lessened in all CLR groups. Overall, ethanol extract from CLR seemed to be more effective than aqueous extracts in improving insulin resistance, resulted in elevating insulin sensitivity, adjusting glucose and lipid metabolism, correcting cytokines levels and ameliorating liver function, especially protecting the liver against lipoid degeneration.

Hypoglycemic Effects and Mechanisms of Action of &lt;i&gt;Cortex Lycii Radicis&lt;/i&gt; on Alloxan-Induced Diabetic Mice

Cortex Lycii Radicis (CLR) has been used as a traditional Oriental medicine as an antipyretic and to treat pneumonia, night-sweats, cough, hematemesis, inflammation, and diabetes mellitus for centuries. This study aimed to determine the effects of CLR on alloxan-induced diabetic mice and its mechanisms. Based on thin-layer chromatography (TLC) assay, the main compounds of CLR include an organic acid, flavone, alkaloid, polysaccharide, anthraquinone, and saponin. The mice were divided into four groups: normal control (NC), diabetes control (DC), diabetes+high-dose CLR (200 mg kg(-1)), and diabetes+low-dose CLR (100 mg kg(-1)). The diabetic mice were administered CLR daily for 28 days. The CLR treatment resulted in significant decreases in fasting blood glucose, total cholesterol, and triglycerides. CLR also showed a tendency to improve body weight gain in diabetic mice. Furthermore, the serum insulin level of each group was assayed, and the DC group had a lower serum insulin level than the NC group. Insulin levels were dose dependently raised in the CLR-treated groups compared with the DC group. According to single-cell gel electrophoresis and LD(50) analysis, CLR was nontoxic to the animals. The results indicate that CLR alleviates the blood glucose and lipid increases associated with diabetes and improves the abnormal glucose metabolism and increases insulin secretion by restoring impaired pancrease beta-cells in alloxan-induced diabetic mice. The results suggest that CLR has hypoglycemic potential and could be useful in diabetes therapy.

Effects of crude drugs on glucose uptake in 3T3-L1 adipocytes.

In this study, various water-extracted crude drugs from Radix Asparagi, Radix Ginseng, Radix Scutellariae, Cortex Lycii Radicis, Cortex Phellodendri and Radix Ophiopogonis were investigated in their effects on [3H]-2-deoxyglucose uptake in 3T3-L1 adipocytes. Following treatment of cells with various crude drugs for 60 mim, the basal [3H]-2-deoxyglucose uptake in cultured 3T3-L1 cells was changed by Radix Asparagi from 140 pmole/min/mg protein of control to 513 (0.1 mg/ml), 201 (1 mg/ml) and 97 (10 mg/ml). Glucose uptake was changed to 324 (0.1 mg/ml), 146 (1 mg/ml) and 46 (10 mg/ml) with Radix Ginseng. In the presence of Radix Scutellariae, glucose uptake was changed to 215 (0.1 mg/ml), 213 (1 mg/ml) and 34 (10 mg/ml). In the presence of Cortex Lycii Radicis, glucose uptake was 230 (0.1 mg/ml), 188 (1 mg/ml) and 38 (10 mg/ml). In the case of Cortex Phellodendri and Radix Ophiopogonis, uptake was changed to 142 (0.1 mg/ml), 132 (1 mg/ml), 24 (10 mg/ml) and 489 (0.1 mg/ml), 374 (1 mg/ml), 344 (10 mg/ml), respectively. In insulin-stimulated cells, the [3H]-2-deoxyglucose uptake was changed by Radix Asparagi from 570 pmole/min/mg protein of the control to 816 (0.1 mg/ml), 674 (1 mg/ml) and 532 (10 mg/ml). After incubation with Radix Ginseng, the glucose uptake was changed to 254 (0.1 mg/mi), 123 (1 mg/mi) to 76 (10 mg/mi). In the presence of Radix Scutellariae, the glucose uptake was changed to 315 (0.1 mg/ml), 265 (1 mg/ml) and 33 (10 mg/ml). After incubation of Cortex Lycii Radicis, the uptake activity was changed to 281 (0.1 mg/ml), 248 (1 mg/ml) and 37 (10 mg/ml). In the case of Cortex Phellodendri and Radix Ophiopogonis, the activity of glucose uptake was measured as 747 (0.1 mg/ml), 523 (1 mg/ml), 33 (10 mg/ml) and 753 (0.1 mg/ml), 740 (1 mg/ml), and 421 (10 mg/ml), respectively. These results indicate that the water-extracted materials of Radix Asparagi and Radix Ophiopogonis increase the glucose uptake in basal and insulin-stimulated 3T3-L1 adipocytes.

Structures of anti-ace and -renin peptides from lycii radicis cortex

Two novel octapeptides, lyciumins A and B, have been isolated from Lycii Radicis Cortex as anti-ACE and -renin substances and their structures have been established.