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Biomolecules Feb 2022Bone diseases such as osteoporosis are the result of osteoclast over-activation. There are many therapeutic agents from natural compounds inhibiting the formation of...
Bone diseases such as osteoporosis are the result of osteoclast over-activation. There are many therapeutic agents from natural compounds inhibiting the formation of osteoclast that have been reported and are continuously being interested. Amygdalin (AD) is isolated from seeds of L. which has many pharmaceutical effects; however, the effect of AD on osteoclast formation and function remains unknown. Therefore, the underlying mechanism of AD on RANKL-induced osteoclast in RAW 264.7 cells was investigated. Molecular docking simulation revealed that AD can bind to the active sites of RANKL with negative binding affinities. Through TRAP activity, bone resorption, and migration, AD effectively inhibited osteoclast differentiation and function. Expression of transcription factors, such as NFATc1, c-fos, and osteospecific genes (including , , , and results) showed an osteoclast differentiated inhibitory effect by AD treatment. In addition, RANKL-induced activation of MAPK, ER stress, and ROS levels in RANKL-induced osteoclast was significantly inhibited while antioxidant enzymes were recovered in the presence of AD. These results suggest that AD may be a potential candidate derived from natural sources for the treatment of osteoclast bone-related diseases.
Topics: Amygdalin; Cell Differentiation; Down-Regulation; Molecular Docking Simulation; NFATC Transcription Factors; Osteoclasts
PubMed: 35204757
DOI: 10.3390/biom12020256 -
AMB Express Mar 2019The aim of the present study was to evaluate the protective effects of combined atorvastatin and amygdalin in a rat model of endometriosis. Tumor necrosis factor-α...
Synergistic and protective effect of atorvastatin and amygdalin against histopathological and biochemical alterations in Sprague-Dawley rats with experimental endometriosis.
The aim of the present study was to evaluate the protective effects of combined atorvastatin and amygdalin in a rat model of endometriosis. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2) and MMP-9 levels in the peritoneal fluid were determined. The expression of TNF-α, IL-6, MMP-2, and MMP-9 mRNA, and the levels of lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (Gpx) were measured. Histopathological analysis was also conducted. The results showed that peritoneal TNF-α, IL-6, MMP-2, and MMP-9 levels were reduced by > 50%, and mRNA expression was decreased. Lipid peroxidation was considerably reduced, while GSH, SOD, Gpx, and catalase levels increased by > 40%. Reductions in leukocyte infiltration and fibrosis following treatment were also observed. Thus, our study suggested that combined treatment consisting of atorvastatin and amygdalin attenuates endometriosis. A detailed investigation of molecular mechanism of atorvastatin and amygdalin in endometriosis is needed.
PubMed: 30888523
DOI: 10.1186/s13568-019-0760-2 -
Journal of Inflammation Research 2023Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), in which inflammatory is frequently involved. Amygdalin (AMD) is a naturally occurring...
BACKGROUND
Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), in which inflammatory is frequently involved. Amygdalin (AMD) is a naturally occurring compound that exerts anti-fibrotic, anti-inflammatory, analgesic, and immunomodulatory effects in various diseases. The purpose of this study was to investigate the therapeutic effects and molecular mechanisms of AMD on Lumbar spine instability (LSI)-induced IDD in mice.
METHODS
In this study, we first explored the effects of AMD in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old male C57BL/6J mice were administrated with AMD. At 10 weeks after LSI, spinal were collected for tissue analyses, including histology, micro-CT, and immunohistochemistry for Col2, Mmp-13, TNF-α, and p-P65. Additionally, we also evaluated the mRNA and protein expression level of p-P65 and p-IKBα after being treated with AMD in vitro.
RESULTS
Histological staining, micro-CT and immunohistochemical analysis showed that AMD treatment significantly inhibited the expression of TNF-α and Mmp-13, increased the expression of Col2 as well as attenuated the calcification of cartilage endplates, eventually to delayed the progression of IDD. Meanwhile, in vivo and in vitro fluorescence imaging revealed that AMD markedly inhibited the AMD significantly inhibited the LSI-induced increase in TNF-α expression and P65and IKBα phosphorylation.
DISCUSSION
Our findings suggest that AMD partly inhibits the activation of NF-κB signaling pathway to reduce the release of inflammatory mediators and delay the degeneration of cartilage endplate in IDD model mice. Therefore, AMD may be a potential candidate for the treatment of IDD.
PubMed: 37600226
DOI: 10.2147/JIR.S415527 -
International Journal of Molecular... Sep 2023Cancer rates are increasing, and cancer is one of the main causes of death worldwide. Amygdalin, also known as vitamin B17 (and laetrile, a synthetic compound), is a... (Review)
Review
Cancer rates are increasing, and cancer is one of the main causes of death worldwide. Amygdalin, also known as vitamin B17 (and laetrile, a synthetic compound), is a cyanogenic glycoside compound that is mainly found in the kernels and pulps of fruits. This compound has been proposed for decades as a promising naturally occurring substance which may provide anticancer effects. This is a comprehensive review which critically summarizes and scrutinizes the available studies exploring the anticancer effect of amygdalin, highlighting its potential anticancer molecular mechanisms as well as the need for a nontoxic formulation of this substance. In-depth research was performed using the most accurate scientific databases, e.g., PubMed, Cochrane, Embase, Medline, Scopus, and Web of Science, applying effective, characteristic, and relevant keywords. There are several pieces of evidence to support the idea that amygdalin can exert anticancer effects against lung, breast, prostate, colorectal, cervical, and gastrointestinal cancers. Amygdalin has been reported to induce apoptosis of cancer cells, inhibiting cancer cells' proliferation and slowing down tumor metastatic spread. However, only a few studies have been performed in in vivo animal models, while clinical studies remain even more scarce. The current evidence cannot support a recommendation of the use of nutritional supplements with amygdalin due to its cyano-moiety which exerts adverse side effects. Preliminary data have shown that the use of nanoparticles may be a promising alternative to enhance the anticancer effects of amygdalin while simultaneously reducing its adverse side effects. Amygdalin seems to be a promising naturally occurring agent against cancer disease development and progression. However, there is a strong demand for in vivo animal studies as well as human clinical studies to explore the potential prevention and/or treatment efficiency of amygdalin against cancer. Moreover, amygdalin could be used as a lead compound by effectively applying recent developments in drug discovery processes.
PubMed: 37762572
DOI: 10.3390/ijms241814270 -
BMC Complementary Medicine and Therapies Sep 2023Sorafenib (Sor) is the only approved multikinase inhibitor indicated for the treatment of HCC. Previous studies have shown that amygdalin (Amy) possesses anticancer...
BACKGROUND
Sorafenib (Sor) is the only approved multikinase inhibitor indicated for the treatment of HCC. Previous studies have shown that amygdalin (Amy) possesses anticancer activities against several cancer cell lines; we suggested that these compounds might disrupt AMPK/mTOR and BCL-2. Therefore, the current study used integrated in vitro and in silico approaches to figure out Amy and Sor's possible synergistic activity in targeting AMPK/mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death in HepG2 cells.
RESULTS
Notably, Amy demonstrated exceptional cytotoxic selectivity against HepG2 cells in comparison to normal WI-38 cells (IC = 5.21 mg/ml; 141.25 mg/ml), respectively. In contrast, WI-38 cells were far more sensitive to the toxicity of Sor. A substantial synergistic interaction between Amy and Sor was observed (CI = 0.56), which was connected to cell cycle arrest at the S and G2/M stages and increased apoptosis and potential necroptosis. Amy and Sor cotreatment resulted in the highest glutathione levels and induction of pro-autophagic genes AMPK, HGMB1, ATG5, Beclin 1, and LC3, suppressed the mTOR and BCL2 anti-apoptotic gene. Finally, the docking studies proposed that Amy binds to the active site of the AMPK enzyme, thus inhibiting its activity. This inhibition of AMPK ultimately leads to inhibition of mTOR and thus induces apoptosis in the HepG2 cells.
CONCLUSION
Although more in vivo research using animal models is needed to confirm the findings, our findings contribute to the evidence supporting Amy's potential anticancer effectiveness as an alternative therapeutic option for HCC.
Topics: Animals; Carcinoma, Hepatocellular; Sorafenib; AMP-Activated Protein Kinases; Amygdalin; Liver Neoplasms; Proto-Oncogene Proteins c-bcl-2; Apoptosis; Cell Line
PubMed: 37726740
DOI: 10.1186/s12906-023-04142-1 -
Pharmaceuticals (Basel, Switzerland) Oct 2022Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of...
Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin's cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 µg.cm.h. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy.
PubMed: 36355478
DOI: 10.3390/ph15111306 -
Pharmacological Research Oct 2023Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development...
Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.
PubMed: 37722517
DOI: 10.1016/j.phrs.2023.106919 -
Iranian Journal of Basic Medical... Mar 2017Drug delivery across the skin is used for several millennia to ease gastrointestinal (GI) ailments in Traditional Persian Medicine (TPM). TPM topical remedies are... (Review)
Review
Drug delivery across the skin is used for several millennia to ease gastrointestinal (GI) ailments in Traditional Persian Medicine (TPM). TPM topical remedies are generally being applied on the stomach, lower abdomen, lower back and liver to alleviate GI illnesses such as dyspepsia, gastritis, GI ulcers, inflammatory bowel disease, intestinal worms and infections. The aim of the present study is to survey the topical GI remedies and plant species used as ingredients for these remedies in TPM. In addition, pharmacological activities of the mentioned plants have been discussed. For this, we searched major TPM textbooks to find plants used to cure GI problems in topical use. Additionally, scientific databases were searched to obtain pharmacological data supporting the use of TPM plants in GI diseases. and are among the most frequently mentioned ingredients of TPM remedies. β-asarone, amygdalin, boswellic acids, guggulsterone, crocin, crocetin, isomasticadienolic acid, and cyclotides are the most important phytochemicals present in TPM plants with GI-protective activities. Pharmacological studies demonstrated GI activities for TPM plants supporting their extensive traditional use. These plants play pivotal role in alleviating GI disorders through exhibiting numerous activities including antispasmodic, anti-ulcer, anti-secretory, anti-colitis, anti-diarrheal, antibacterial and anthelmintic properties. Several mechanisms underlie these activities including the alleviation of oxidative stress, exhibiting cytoprotective activity, down-regulation of the inflammatory cytokines, suppression of the cellular signaling pathways of inflammatory responses, improving re-epithelialization and angiogenesis, down-regulation of anti-angiogenic factors, blocking activity of acetylcholine, .
PubMed: 28392893
DOI: 10.22038/ijbms.2017.8349 -
Experimental and Therapeutic Medicine Apr 2018The aim of the present study was to elucidate the mechanism of amygdalin treatment on reducing liver fibrosis by investigating its role in regulating the expression...
The aim of the present study was to elucidate the mechanism of amygdalin treatment on reducing liver fibrosis by investigating its role in regulating the expression level of platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and PDGF receptor (PDGFR) in the hepatic stellate cell (HSC)-T6 line. HSC-T6 cells were used as an model and randomly assigned into four groups: control, high-dose amygdalin, mid-dose amygdalin and low-dose amygdalin. Following amygdalin treatment, compared with the control, a high dose of amygdalin significantly suppressed the mRNA expression of PDGF and IGF (each P<0.05), whereas moderate and low doses showed no significant effect, relatively low doses of amygdalin are not sufficient to transfer signals to its receptor. The high-dose amygdalin and low-dose amygdalin displayed suppressed protein expression of PDGF at 24, 48 and 72 h, with the high-dose group exhibiting the most marked suppression at all three time points. By reducing the transcription of PDGF and IGF mRNA and the expression of PDGF protein, amygdalin decreased the synthesis and release of PDGF and IGF, thereby reducing the influence of PDGF and IGF on HSCs, thus protecting the liver from fibrosis.
PubMed: 29556259
DOI: 10.3892/etm.2018.5886 -
Journal of Cancer Research and... Aug 2014Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by... (Review)
Review
Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by World Health Organization (WHO). In recent years the development of antitumor drugs has been gradually transformed from cytotoxic drugs to improving the selectivity of drugs, overcoming multidrug resistance, development of new targeted drugs and low toxicity with high specificity drugs. Amygdalin is a natural product that owns antitumor activity, less side effects, widely sourced and relatively low priced. All these features make the amygdalin a promising antitumor drugs, if combined with conditional chemotherapy drugs, which can produce synergistic effect. In this paper, we summarized the pharmacological activity, toxicity and antitumor activity of amygdalin, mainly focused on the advanced research of amygdalin on its antitumor effects in recent years, providing new insights for the development of new anticancer drugs, new targets searching and natural antitumor mechanism investigations.
Topics: Amygdalin; Antineoplastic Agents; Apoptosis; Humans; Neoplasms
PubMed: 25207888
DOI: 10.4103/0973-1482.139743