Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.
Albumins ; Animals ; Blood Glucose ; metabolism ; Creatinine ; blood ; Diabetic Nephropathies ; blood ; drug therapy ; genetics ; urine ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad Proteins ; genetics ; metabolism ; Taxus ; chemistry ; Transforming Growth Factor beta1 ; metabolism

Taxol is one of the most important chemotherapeutic drugs against cancer. Taxol has been mainly extracted from the bark of yews for a long time. However, methods for the extraction of taxol from the bark of Taxus species were inefficient and environmentally costly. As a result of the high ecological toll exacted on trees with the potential for Pacific yew extinction, investigators began to look for other methods of taxol production. Recently, increasing efforts have been made to develop alternative means of taxol production, such as using complete chemical synthesis, semi-synthesis, Taxus spp. plant cell culture and microbe fermentation. Using microbe fermentation in the production of taxol would be a very prospective method for obtaining a large amount of taxol. Therefore, it is necessary to understand the molecular basis and genetic regulation mechanisms of taxol biosynthesis by endophytic fungi, which may be helpful to construct the genetic engineering strain with high taxol output. In this paper, the taxol biosynthesis pathway from Taxus cells and the advantages of taxol biosynthesis by endophytic fungi were discussed. The study on the isolation and biodiversity of taxol-producing endophytic fungi and the taxol biosynthesis related genes are also discussed.
Endophytes ; Fungi ; Industrial Microbiology ; Microorganisms, Genetically-Modified ; Neoplasms ; drug therapy ; Paclitaxel ; biosynthesis ; Taxus ; chemistry

Plants synthesize certain phytoconstituents for their protection, which, because they are not of primary need, are known as secondary metabolites. These secondary metabolites of plants, have often been found to have medicinal uses for human beings. One such gymnosperm having secondary metabolites of medicinal potential for humans is Taxus wallichiana (Himalayan yew). Besides being the source of taxol, this plant has been investigated for its essential oil, diterpenoids, lignans, steroids, sterols and biflavonoids. Traditionally, it is used to treat disorders of the digestive, respiratory, nervous and skeletal systems. Although pharmacologically underexplored, it has been used for antiepileptic, anti-inflammatory, anticancer, antipyretic, analgesic, immunomodulatory and antimicrobial activities. The present review compiles traditional uses, phytochemical constituents (specifically the secondary metabolites) pharmacological activities and the toxicity of T. wallichiana.
Ethnopharmacology ; Humans ; Phytotherapy ; Plant Preparations ; chemistry ; pharmacology ; Plant Structures ; Plants, Medicinal ; Taxus ; chemistry

The chemical constituents of Taxus chinensis var. mairei cell cultures were investigated by chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from the 80% ethanol extract of cultured cells and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2α,4α,7β,9α,10β-pentaacetoxy-14β-hydroxytax-11-ene (1), 2α,4α,7β,9α,10β-pentaacetoxytax-11-ene (2), 1β-deoxybaccatin VI (3), 2α-acetoxytaxusin (4), taxuyunnanine C (5), yunnanxane (6), 2α,5α,10β-triacetoxy-14β-propionyloxy-4 (20), 11-taxadiene (7), 2α,5α,10β-triacetoxy-14β-isobutyryloxy-4 (20), 11-taxadiene (8), 2α,5α,10β-triacetoxy-14β-(2'-methyl)butyryloxy-4 (20), 11-taxadiene (9), 13-dehydroxylbaccatin III (10), 13-dehydroxy-10-deacetylbaccatin III (11), paclitaxel (12) and (13) β-sitosterol. Among them, compound 1 is a new compound, and compounds 2, 4, 10 and 11 are isolated from the cell culture of Taxus chinensis var. mairei for the first time.
Alkenes ; analysis ; Cell Culture Techniques ; Cells, Cultured ; Diterpenes ; analysis ; Molecular Structure ; Paclitaxel ; analysis ; Sitosterols ; analysis ; Taxoids ; analysis ; Taxus ; chemistry

Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
Animals ; Bridged-Ring Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Plant Extracts ; chemical synthesis ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Taxoids ; chemical synthesis ; chemistry ; pharmacology ; Taxus ; chemistry

OBJECTIVETo observe the effects of acupuncture at "Feishu" (BL 13) and "Lingtai" (GV 10) on distribution taxis of paclitaxel in mice with lung cancer to discuss targeted relationship between acupoints and corresponding viscera.

METHODSAccording to randomized digital table, 315 SPF-grade BALB/C female mice were divided into 7 groups: blank group (group A), model group (group B), medication group (group C), acupuncture at non-acupoint group (group D), acupuncture at Feishu group (group E), acupuncture at Lingtai group (group F) and acupuncture at Feishu and Lingtai group (group G), 45 mice in each one. Except the blank group, the remaining groups were treated with N-nitroso-tris-chloroethyl urea (NTCU) to establish the model of squamous-cell carcinoma. After model establishment, group A, group B and group C were not treated with acupuncture; group A and group B were treated with intraperitoneal injection of 0.9% sodium chlorvde solution by 6 mL/kg while group C was treated with intraperitoneal injection of paclitaxel by 6 mL/kg. The group D, group E, group F and group G were treated with acupuncture at non-acupoint, "Feishu" (BL 13), "Lingtai" (GV 10) and "Feishu" (BL 13) plus "Lingtai" (GV 10), respectively, then were intraperitoneally injected with paclitaxel by 6 mL/kg. The treatment was all given once a day for continuous 10 days. 15 min, 30 min, 1 h, 2 h, 8 h, 12 h and 24 h after the treatments, 6 mice in each group were randomly selected and sacrificed to collect samples of lung, liver, spleen, kidney and heart, etc. High performance liquid chromatography was applied to measure the concentration of paclitaxel in each organ (lung, liver, spleen, kidney and heart) at different time points.

RESULTS(1) The content of paclitaxel in lung, kidney and heart reached the peak at 2 h, then decreased significantly in group C, group D, group E, group F and group G; the content of paclitaxel in spleen showed downtrend at each time point. The content of paclitaxel in liver reached the peak at 2 h in group C and group D; the content of paclitaxel reached the peak at 8 h in group E, group F and group G. (2) The content of paclitaxel in lung in group E and group G was higher than that in group C and group D at each time point (all P < 0.01); the content of paclitaxel in lung in group F was higher than that in group C (P < 0.01) and group D (P < 0.01) only at time point of 2 h. The content of paclitaxel in lung in group G was higher than that in group F at each time point (all P < 0.05). There was no statistical difference between group G and group E (all P > 0.05).

CONCLUSIONAcupuncture at "Feishu" (BL 13) and "Lingtai" (GV 10) could influ- ence the metabolism of paclitaxel in lung-cancer mice, leading to distribution change in each organ. As a result, it could cause targeting effects, which is more significant at "Feishu" (BL 13) and "Lingtai" (GV 10).

Acupuncture Points ; Acupuncture Therapy ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacokinetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; therapy ; Mice ; Mice, Inbred BALB C ; Paclitaxel ; pharmacokinetics ; Taxus ; chemistry

OBJECTIVETo study the inhibitory effects of Taxus chinensis var. mairei Aqueous Extract (TAE) on SGC-7901 and MCF-7 cells, and to explore its mechanisms.

METHODSThe inhibitory effects of TAT and Paclitaxel on the proliferation of SGC-7901 and MCF-7 cells were tested by MTT method. Their effects on the morphology of SGC-7901 and MCF-7 cells were observed by microscope. Its effects on the cell apoptosis were detected by flow cytometry.

RESULTSThe TAE had inhibitory effects on the proliferation of tumor cells, and its mechanisms were correlated to inducing the apoptosis of tumor cells.

CONCLUSIONTAE had inhibitory effects on the proliferation of tumor cells.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; MCF-7 Cells ; Plant Extracts ; pharmacology ; Taxus ; chemistry

OBJECTIVETo study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) on the growth of A549 lung cancer xenografts in nude mice and its mechanism.

METHODThe A549 lung cancer xenograft model was established, and then randomly divided into the control group, and low, middle and high dose AETC experiment groups. After 24 hours, they were orally administered with normal saline and drugs of the same volume for seven weeks. The length and width of the xenografts were measured every three days, and the xenograft growth curve was drawn. The nude mice were sacrificed after the administration for seven weeks, and their xenografts were collected to cultivate the anti-tumor rate. Real-time PCR and Western-blot were adopted to detect mRNA and protein levels.

RESULTAll of AETC experiment groups showed a significant anti-tumor effect (P < 0.05). Compared with the control group, each experimental group showed notable reduction in EGFR and Survivin mRNA in xenograft tissues (P < 0.05), with no significant change in VEGF mRNA level. The analysis on gray value ratio showed that EGFR mRNA were down-regulated (P < 0.05) in xenograft tissues in all experimental groups, but with no statistical significance in difference, and Survivin and p-EGFR were significantly down-regulated.

CONCLUSIONAETC has not significant effect on angiogenesis, but may have the inhibitory effect on xenograft growth by inhibiting Survivin protein and EGFR phosphorylation.

Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Growth Inhibitors ; administration & dosage ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; Mice ; Taxus ; chemistry ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Xenograft Model Antitumor Assays

Taxus is the source plant of anti-cancer drug paclitaxel and its biosynthetic precursor, analogs and derivatives, which has been studying for decades. There are many endemic Taxus species in China, which have been studied in the field of multiple disciplines. Based on the recent studies of the researchers, this review comments on the study of Taxus biology and chemistry. The bibliometric method is used to quantify the global scientific production of Taxus-related research, and identify patterns and tendencies of Taxus-related articles. Gaps are present in knowledge about the genomics, epigenomics, transcriptomics, proteomics, metabolomics and bioinformatics of Taxus and their endophytic fungi. Systems biology and various omics technologies will play an increasingly important role in the coming decades.
Computational Biology ; Endophytes ; chemistry ; isolation & purification ; Epigenomics ; methods ; Fungi ; chemistry ; isolation & purification ; Gene Expression Profiling ; Genomics ; methods ; Metabolomics ; Molecular Biology ; Paclitaxel ; biosynthesis ; chemistry ; isolation & purification ; Phylogeny ; Plants, Medicinal ; chemistry ; classification ; genetics ; microbiology ; Proteomics ; Systems Biology ; Taxus ; chemistry ; classification ; genetics ; microbiology