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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 -
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 -
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 -
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 -
Cells Mar 2024Inflammatory bowel disease (IBD) refers to a cluster of intractable gastrointestinal disorders with an undetermined etiology and a lack of effective therapeutic agents....
Inflammatory bowel disease (IBD) refers to a cluster of intractable gastrointestinal disorders with an undetermined etiology and a lack of effective therapeutic agents. Amygdalin (Amy) is a glycoside extracted from the seeds of apricot and other plants and it exhibits a wide range of pharmacological properties. Here, the effects and mechanisms of Amy on colitis were examined via 16S rRNA sequencing, ELISA, transmission electron microscopy, Western blot, and immunofluorescence. The results showed that Amy administration remarkably attenuated the signs of colitis (reduced body weight, increased disease activity index, and shortened colon length) and histopathological damage in dextran sodium sulfate (DSS)-challenged mice. Further studies revealed that Amy administration significantly diminished DSS-triggered gut barrier dysfunction by lowering pro-inflammatory mediator levels, inhibiting oxidative stress, and reducing intestinal epithelial apoptosis and ferroptosis. Notably, Amy administration remarkably lowered DSS-triggered TLR4 expression and the phosphorylation of proteins related to the NF-κB and MAPK pathways. Furthermore, Amy administration modulated the balance of intestinal flora, including a selective rise in the abundance of and a decline in the abundance of , , , , and . In conclusion, Amy can alleviate colitis, which provides data to support the utility of Amy in combating IBD.
Topics: Animals; Mice; Amygdalin; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Colitis; Cell Death; Inflammatory Bowel Diseases; Dextran Sulfate
PubMed: 38474407
DOI: 10.3390/cells13050444 -
BMC Plant Biology Jun 2024The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed...
BACKGROUND
The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed amygdalin content of P. sibirica is an interesting question. Mandelonitrile is known as one key intermediate of amygdalin metabolism, but which mandelonitrile lyase (MDL) family member essential for its dissociation destined to low amygdalin accumulation in P. sibirica seeds still remains enigmatic. An integration of our recent 454 RNA-seq data, amygdalin and mandelonitrile content detection, qRT-PCR analysis and function determination is described as a critical attempt to determine key MDL and to highlight its function in governing mandelonitrile catabolism with low amygdalin accumulation in Prunus sibirica seeds for better developing edible oil and biodiesel in China.
RESULTS
To identify key MDL and to unravel its function in governing seed mandelonitrile catabolism with low amygdalin accumulation in P. sibirica. Global identification of mandelonitrile catabolism-associated MDLs, integrated with the across-accessions/developing stages association of accumulative amount of amygdalin and mandelonitrile with transcriptional level of MDLs was performed on P. sibirica seeds of 5 accessions to determine crucial MDL2 for seed mandelonitrile catabolism of P. sibirica. MDL2 gene was cloned from the seeds of P. sibirica, and yeast eukaryotic expression revealed an ability of MDL2 to specifically catalyze the dissociation of mandelonitrile with the ideal values of K (0.22 mM) and V (178.57 U/mg). A combination of overexpression and mutation was conducted in Arabidopsis. Overexpression of PsMDL2 decreased seed mandelonitrile content with an increase of oil accumulation, upregulated transcript of mandelonitrile metabolic enzymes and oil synthesis enzymes (involving FA biosynthesis and TAG assembly), but exhibited an opposite situation in mdl2 mutant, revealing a role of PsMDL2-mediated regulation in seed amygdalin and oil biosynthesis. The PsMDL2 gene has shown as key molecular target for bioengineering high seed oil production with low amygdalin in oilseed plants.
CONCLUSIONS
This work presents the first integrated assay of genome-wide identification of mandelonitrile catabolism-related MDLs and the comparative association of transcriptional level of MDLs with accumulative amount of amygdalin and mandelonitrile in the seeds across different germplasms and developmental periods of P. sibirica to determine MDL2 for mandelonitrile dissociation, and an effective combination of PsMDL2 expression and mutation, oil and mandelonitrile content detection and qRT-PCR assay was performed to unravel a mechanism of PsMDL2 for controlling amygdalin and oil production in P. sibirica seeds. These findings could offer new bioengineering strategy for high oil production with low amygdalin in oil plants.
Topics: Amygdalin; Prunus; Seeds; Plant Proteins; Plant Oils; Aldehyde-Lyases; Gene Expression Regulation, Plant
PubMed: 38902595
DOI: 10.1186/s12870-024-05300-4 -
Journal of Microbiology and... Oct 2023Infectious diseases caused by drug-resistant () pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study,...
Infectious diseases caused by drug-resistant () pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study, amygdalin exhibited anti-inflammatory and antioxidant activities, as well as other potentials. However, whether it could influence the drug-resistant -infected cells remained unanswered. Amygdalin was therefore tested in a cellular model in which human macrophages were exposed to resistant . Apoptosis was measured by flow cytometry and the lactate dehydrogenase (LDH) assay. Western immunoblotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to quantify interleukin-18 (IL-18), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The production of reactive oxygen species (ROS) in macrophages was detected by ROS kit. The expression of panapoptotic proteins in macrophages was measured by qRT-PCR and Western immunoblotting. Drug-Resistant inhibited cell viability and enhanced apoptosis in the cellular model. In cells treated with amygdalin, this compound can inhibit cell apoptosis and reduce the expression of pro - inflammatory cytokines such as IL-1β, IL-18 and IL-6. Additionally, it decreases the production of PANoptosis proteins, Furthermore, amygdalin lowered the levels of reactive oxygen species induced by drug-resistant , in cells, demonstrating its antioxidant effects. Amygdalin, a drug with a protective role, alleviated cell damage caused by drug-resistant in human macrophages by inhibiting the PANoptosis signaling pathway.
Topics: Humans; Amygdalin; Interleukin-6; Interleukin-18; Escherichia coli; Reactive Oxygen Species; Macrophages
PubMed: 37559205
DOI: 10.4014/jmb.2306.06030 -
Iranian Journal of Allergy, Asthma, and... Oct 2023Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable...
Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)-dendritic cell (DC)-OX40L axis was investigated. A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively. Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased. Amygdalin thus regulates the Th1/Th2 balance through the TSLP-DC-OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments.
Topics: Mice; Animals; Child; Humans; Thymic Stromal Lymphopoietin; Interleukin-13; Amygdalin; OX40 Ligand; Interleukin-4; Interleukin-5; Cytokines; Asthma; Disease Models, Animal; Inflammation; Th2 Cells; Dendritic Cells; Mice, Inbred BALB C
PubMed: 38085145
DOI: 10.18502/ijaai.v22i5.13993 -
Molecular Biology Reports Nov 2023A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this...
BACKGROUND
A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias.
AIM
this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol.
METHODS
Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations.
RESULTS
Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts.
CONCLUSION
Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.
Topics: Rats; Animals; Stomach Ulcer; Ulcer; Propolis; Amygdalin; Histamine; Plant Extracts; Anti-Ulcer Agents; Gastric Mucosa; Omeprazole; Ethanol
PubMed: 37741810
DOI: 10.1007/s11033-023-08776-9 -
PeerJ 2023L. (mahlab cherry) is a deciduous plant that is native to the Mediterranean region and central Europe with a myriad of medicinal, culinary and cosmetic uses. The...
Profiling of primary and phytonutrients in edible mahlab cherry ( L.) seeds in the context of its different cultivars and roasting as analyzed using molecular networking and chemometric tools.
L. (mahlab cherry) is a deciduous plant that is native to the Mediterranean region and central Europe with a myriad of medicinal, culinary and cosmetic uses. The present study explored different cultivars of mahlab (white from Egypt and Greece, red from Egypt and post roasting). UPLC-MS led to the detection of 110 primary and secondary metabolites belonging to different classes including phenylpropanoids (hydroxy cinnamates, coumaroyl derivatives), organic acids, coumarins, cyanogenic glycosides, flavonoids, nitrogenous compounds, amino acids and fatty acids, of which 39 are first time to be detected in L. A holistic assessment of metabolites was performed for further analysis of dataset using principal component analysis (PCA) among mahlab cultivars to assess variance within seeds. The results revealed that phenolic acids (coumaric acid--hexoside, ferulic acid--hexoside, ferulic acid--hexoside dimer, dihydrocoumaroyl--hexoside dimer and ferulic acid), coumarins (coumarin and herniarin) and amino acids (pyroglutamic acid) were abundant in white mahlab cultivars (cvs.) from different locations. In contrast, red mahlab and its roasted seeds were more rich in organic acids (citric and malic acids), amygdalin derivative and sphingolipids. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed for markers in red mahlab and in response to roasting, where red mahlab was rich in nitrogenous compounds viz. nonamide, deoxy fructosyl leucine, glutaryl carnitine and isoleucine, while roasted product (REM) was found to be enriched in choline.
Topics: Prunus; Chemometrics; Chromatography, Liquid; Tandem Mass Spectrometry; Seeds; Prunus avium; Amino Acids; Phytochemicals; Antifibrinolytic Agents
PubMed: 37663279
DOI: 10.7717/peerj.15908