Pair Name	Biochanin A, SB590885
Phytochemical Name	Biochanin A
Anticancer drug Name	SB590885
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The results identify an effective combination therapy for the most aggressive form of HCC and provide the possibility of therapeutic improvement for patients with advanced HCC.

Pair Name	Corilagin, Paclitaxel
Phytochemical Name	Corilagin
Anticancer drug Name	Paclitaxel
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our observations indicate that corilagin sensitized epithelial ovarian cancer cells to paclitaxel and carboplatin treatment by primarily inhibiting Snail-glycolysis pathways. Corilagin is a herbal medicine with low toxic effects to normal cells, particularly hepatoprotective, and may be an ideal complimentary medicine when combined with highly toxic chemotherapeutic agents.

Pair Name	Curcumin, Fluorouracil
Phytochemical Name	Curcumin
Anticancer drug Name	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	We conclude that curcumin promotes chemosensitivity of CRC cells to 5-FU by downregulating L1 expression. Our findings provide experimental evidence for the synergism between curcumin and 5-FU, which can be utilized in clinical applications for reducing the toxicity and adverse effects of 5-FU.

Pair Name	Narirutin, Cisplatin
Phytochemical Name	Narirutin
Anticancer drug Name	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Based on the significant anticancer effect and high biosafety, naringin has great potential as a functional food in the adjuvant treatment of lung cancer.

Pair Name	Paeonol, Epirubicin
Phytochemical Name	Paeonol
Anticancer drug Name	Epirubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	These findings suggest that combination of Paeonol and Epirubicin is potentially applicable for breast cancer treatment.

Pair Name	Trifolirhizin, Sorafenib
Phytochemical Name	Trifolirhizin
Anticancer drug Name	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	Synergistic anticancer effect of flavonoids from Sophora alopecuroides with Sorafenib against hepatocellular carcinoma

Pair Name	Umbelliferone, Cisplatin
Phytochemical Name	Umbelliferone
Anticancer drug Name	Cisplatin
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Combination of 7-hydroxycoumarin in a platinum(IV) complex derived from cisplatin enhanced cytotoxicity with multiple mechanisms of action.

Pair Name	(S)-10-Hydroxycamptothecin, Crizotinib
Phytochemical	(S)-10-Hydroxycamptothecin
Drug	Crizotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Development of 10-Hydroxycamptothecin-crizotinib conjugate based on the synergistic effect on lung cancer cells

Pair Name	10-Gingerol, Paclitaxel
Phytochemical	10-Gingerol
Drug	Paclitaxel
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.

Pair Name	Acteoside, Temozolomide
Phytochemical	Acteoside
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	It was also determined that TMZ + acteoside induced apoptosis and autophagy through the mitogen‑activated protein kinase signaling pathway. These findings suggest that acteoside has beneficial effects on TMZ‑based glioblastoma therapy.

Pair Name	All-trans retinoic acid, Midostaurin
Phytochemical	All-trans-retinoic acid
Drug	Midostaurin
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Combination of midostaurin and ATRA exerts dose-dependent dual effects on acute myeloid leukemia cells with wild type FLT3

Pair Name	alpha-Mangostin, Sorafenib
Phytochemical	alpha-Mangostin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

Pair Name	alpha-Mangostin, Sorafenib
Phytochemical	alpha-Mangostin
Drug	Sorafenib
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These data demonstrate an unanticipated synergy between α-Mangostin and sorafenib, with mechanistic actions that convert a known safe natural product to a candidate combinatorial therapeutic agent.

Pair Name	Amentoflavone, Sorafenib
Phytochemical	Amentoflavone
Drug	Sorafenib
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Amentoflavone may sensitize OS to sorafenib treatment by inducing intrinsic and extrinsic apoptosis and inhibiting ERK/NF-κB signaling transduction.

Pair Name	Apigenin, Doxorubicin
Phytochemical	Apigenin
Drug	Doxorubicin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Co-administration of apigenin with doxorubicin enhances anti-migration and antiproliferative effects via PI3K/PTEN/AKT pathway in prostate cancer cells

Pair Name	Baicalein, Cisplatin
Phytochemical	Baicalein
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Treatment with baicalein improved the sensitivity of ovarian cancer cells to cisplatin and inhibited cell proliferation, metastasis and tumor growth

Pair Name	Berbamine, Arcyriaflavin A
Phytochemical	Berbamine
Drug	Arcyriaflavin A
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our findings suggest that a novel combination therapy involving berbamine and ArcA could effectively eradicate glioblastoma stem-like cells.

Pair Name	Berbamine, Sorafenib
Phytochemical	Berbamine
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Targeting Na+/K+-ATPase by berbamine and ouabain synergizes with sorafenib to inhibit hepatocellular carcinoma

Pair Name	Berberine, Cisplatin
Phytochemical	Berberine
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Berberine and Cisplatin Exhibit Synergistic Anticancer Effects on Osteosarcoma MG-63 Cells by Inhibiting the MAPK Pathway

Pair Name	Berberine, Erlotinib
Phytochemical	Berberine
Drug	Erlotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our data supported use of BBR in combination with erlotinib as a novel strategy for treatment of patients with EGFR positive tumors.

Pair Name	Beta-Elemene, Fluorouracil
Phytochemical	Beta-Elemene
Drug	Fluorouracil
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The conclusion obtained, considering that the results suggest that the combination may be important specifically in the treatment of TNBC.

Pair Name	Caffeic acid, Paclitaxel
Phytochemical	Caffeic acid
Drug	Paclitaxel
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.

Pair Name	Chebulagic acid, Doxorubicin
Phytochemical	Chebulagic acid
Drug	Doxorubicin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Activity
Result	The present study shows the efficacy of CA to overcome MDR-1 mediated drug resistance in HepG2 cells through COX-2 dependant modulation of MDR-1.

Pair Name	Chlorogenic acid, Doxorubicin
Phytochemical	Chlorogenic acid
Drug	Doxorubicin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility.

Pair Name	Chlorogenic acid, Fluorouracil
Phytochemical	Chlorogenic acid
Drug	Fluorouracil
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	CGA sensitizes hepatocellular carcinoma cells to 5-FU treatment by the suppression of ERK activation through the overproduction of ROS. CGA has shown potential as a chemosensitizer of 5-FU chemotherapy in hepatocellular carcinoma.

Pair Name	Costunolide, Osimertinib
Phytochemical	Costunolide
Drug	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.

Pair Name	Cryptotanshinone, Trifluridine
Phytochemical	Cryptotanshinone
Drug	Trifluridine
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	FTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

Pair Name	Curcumin, TNF-related apoptosis inducing ligand
Phytochemical	Curcumin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. The synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-kappaB via inhibition of the Akt/IKKalpha pathway and enhanced ERK1/2 activity

Pair Name	Curcumin, Vemurafenib
Phytochemical	Curcumin
Drug	Vemurafenib
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Curcumin suppresses cell proliferation and triggers apoptosis in vemurafenib-resistant melanoma cells by downregulating the EGFR signaling pathway

Pair Name	Daidzein, Gefitinib
Phytochemical	Daidzein
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	Daidzein Synergizes with Gefitinib to Induce ROS/JNK/c-Jun Activation and Inhibit EGFR-STAT/AKT/ERK Pathways to enhance Lung Adenocarcinoma cells chemosensitivity

Pair Name	Daurinoline, Sorafenib
Phytochemical	Daurinoline
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC.

Pair Name	Decursin, Doxorubicin
Phytochemical	Decursin
Drug	Doxorubicin
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

Pair Name	Emodin, Cytarabine
Phytochemical	Emodin
Drug	Cytarabine
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Emodin and its combination with Ara-C may be considered a promising therapeutic approach in AML and worthy of further investigation.

Pair Name	Evodiamine, Doxorubicin
Phytochemical	Evodiamine
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our results indicated that EVO enhanced the apoptotic action of DOX by inhibiting the Ras/MEK/ERK cascade and the expression of IAPs without inhibiting the expression and activity of P-glycoprotein (P-gp). Taken together, our data indicate that EVO, a natural product, may be useful applied alone or in combination with DOX for the treatment of resistant breast cancer.

Pair Name	Gambogenic acid, Erlotinib
Phytochemical	Gambogenic acid
Drug	Erlotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our findings provide preclinical evidence for using GNA as an FGFR signaling pathway inhibitor to overcome erlotinib resistance in NSCLC treatment or to enhance erlotinib efficacy when used as a combined administration.

Pair Name	Gambogic Acid, Cisplatin
Phytochemical	Gambogic Acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	Gambogic acid sensitises lung cancer cells to CDDP in vitro and in vivo in NSCLC through inactivation of NF-κB and MAPK/HO-1 signalling pathways, providing a rationale for the combined use of CDDP and GA in lung cancer chemotherapy.

Pair Name	Gambogic Acid, Gemcitabine
Phytochemical	Gambogic Acid
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.

Pair Name	Gedunin, Epalrestat
Phytochemical	Gedunin
Drug	Epalrestat
Disease Info	[ICD-11: 2B66.Z]	Oral cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	Our results provide compelling evidence that the combination of gedunin and epalrestat modulates expression of key oncogenic signalling kinases and transcription factors primarily by influencing phosphorylation and subcellular localisation. AR inhibitors such as gedunin and epalrestat are novel candidate agents for cancer prevention and therapy.

Pair Name	Ginkgolide B, Cisplatin
Phytochemical	Ginkgolide B
Drug	Cisplatin
Disease Info	[ICD-11: 2B66.Z]	Oral cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These results suggest that PAFR is a therapeutic target for modulating CDDP sensitivity in OSCC cells. Thus, GB may be a novel drug that could enhance combination chemotherapy with CDDP for OSCC patients.

Pair Name	Ginsenoside Rg1, Doxorubicin
Phytochemical	Ginsenoside Rg1
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	The present results support the chemosensitizing property of ginsenoside Rg1 in triple-negative breast cancer cell lines.

Pair Name	Gossypol, Gefitinib
Phytochemical	Gossypol
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations.

Pair Name	Halofuginone, Cisplatin
Phytochemical	Halofuginone
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

Pair Name	Honokiol, Oxaliplatin
Phytochemical	Honokiol
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	This combination allows a reduction in oxaliplatin dose, and thereby reduces its adverse effects. It may also enhance the chemotherapeutic effect of oxaliplatin for this disease.

Pair Name	Kaempferol, Erlotinib
Phytochemical	Kaempferol
Drug	Erlotinib
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These data imply that KAE may be a valid therapeutic candidate to potentiate PC cell sensitivity to ERL via inhibiting PI3K/AKT and EGFR signaling.

Pair Name	Licochalcone B, TNF-related apoptosis inducing ligand
Phytochemical	Licochalcone B
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

Pair Name	Luteolin, Oxaliplatin
Phytochemical	Luteolin
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Luteolin potentiates low-dose oxaliplatin-induced inhibitory effects on cell proliferation in gastric cancer by inducing G2/M cell cycle arrest and apoptosis

Pair Name	Lycorine, Bortezomib
Phytochemical	Lycorine
Drug	Bortezomib
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	We observed higher HMGB1 expression in bortezomib resistant cells and the combination of bortezomib plus lycorine was highly efficient in vitro and in vivo myeloma models as well as in re-sensitizing resistant cells to bortezomib. These observations indicate lycorine as an effective autophagy inhibitor and reveal that lycorine alone or in combination with bortezomib is a potential therapeutic strategy.

Pair Name	Magnolin, B-RAF Inhibitors
Phytochemical	Magnolin
Drug	B-RAF Inhibitors
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Synergistic activity of magnolin combined with B-RAF inhibitor SB590885 in hepatocellular carcinoma cells via targeting PI3K-AKT/mTOR and ERK MAPK pathway

Pair Name	Morusin, MAPK pathway inhibitors
Phytochemical	Morusin
Drug	MAPK pathway inhibitors
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our results suggested that the combination of morusin and MAPK pathway inhibitors may be a more effective treatment strategy for BRAF-mutant melanoma than MAPK pathway inhibitors alone.

Pair Name	Myriocin, Cisplatin
Phytochemical	Myriocin
Drug	Cisplatin
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	We suggest that myriocin is a novel potent anti-cancer agent that dually targets both VEGFR2 in ECs and IκBα in cancer cells, and exerts more pronounced anti-tumor effects than with either kinase being inhibited alone.

Pair Name	Nobiletin, Bicalutamide
Phytochemical	Nobiletin
Drug	Bicalutamide
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	NBT and BCT combination reduced key cellular signaling regulators including: p-Erk/Erk, p-STAT3/STAT3 and NF-κB. Overall, these results suggest that NBT combination with BCT may be an effective treatment for prostate cancer.

Pair Name	Oleanolic Acid, Gemcitabine
Phytochemical	Oleanolic Acid
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	We found an interesting finding that the 73-03 in combination with GCB can improve GCB efficacy and decrease PCa resistance, which induced apoptosis and mitochondrial damage through epigenetic inhibition of SPINK1 transcription by miR-421 up-regulation. This was the first study that used OA derivatives on GCB-resistant PCa cells, so this combined strategy warrants further investigation.

Pair Name	Oridonin, Fluorouracil
Phytochemical	Oridonin
Drug	Fluorouracil
Disease Info	[ICD-11: 2C90.Z]	Renal carcinoma		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Activity
Result	Oridonin enhances the cytotoxicity of 5-FU in renal cancer cells partially through inducing necroptosis, providing evidence of using necroptosis inducers in combination with chemotherapeutic agents for cancer treatment.

Pair Name	Oxidized tea polyphenol, Nimotuzumab
Phytochemical	Oxidized tea polyphenol
Drug	Nimotuzumab
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	OTP-3 can also serve as an effective therapeutic agent in NSCLC where it can augment the effects of nimotuzumab, a valuable property for combination agents.

Pair Name	Periplocin, TNF-related apoptosis inducing ligand
Phytochemical	Periplocin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway

Pair Name	Platycodin D, Venetoclax
Phytochemical	Platycodin D
Drug	Venetoclax
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Platycodin D may be a potent therapeutic candidate for the treatment of AML

Pair Name	Pterostilbene, Fluorouracil
Phytochemical	Pterostilbene
Drug	Fluorouracil
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These results provide a rationale for novel combination treatment strategies, especially for patients with 5-FU-resistant tumors expressing ER-β protein.

Pair Name	Quercetin, Doxorubicin
Phytochemical	Quercetin
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Que could attenuate AC-induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition,in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC

Pair Name	Resveratrol, Sorafenib
Phytochemical	Resveratrol
Drug	Sorafenib
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	PEGylated resveratrol combined with sorafenib can achieve synergistic anti-RCC activity, and the mechanism may be related to the inhibition of Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Pair Name	Resveratrol, Temozolomide
Phytochemical	Resveratrol
Drug	Temozolomide
Disease Info	[ICD-11: 2F7Z]	Glioma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Activity
Result	TMZ in combination with resveratrol remarkably increased reactive oxygen species (ROS) production, which serves as an upstream signal for AMP-activated protein kinase (AMPK) activation. Subsequently, activated AMPK inhibited mTOR signaling and downregulated antiapoptosis protein Bcl-2, which was contributed to the additive antiproliferation effects of combination treatment. In an orthotopic xenograft model of GBM, TMZ plus resveratrol treatment significantly reduced the volume of tumor, which was confirmed by decreased expression of Ki-67, a marker of proliferation index

Pair Name	Resveratrol, Temozolomide
Phytochemical	Resveratrol
Drug	Temozolomide
Disease Info	[ICD-11: 2F7Z]	Glioma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	TMZ-induced ROS/ERK-mediated autophagy protected glioma cells from apoptosis, and the combination of resveratrol with TMZ could improve the efficacy of chemotherapy for brain tumors.

Pair Name	Retinoic acid, PI3K inhibitor
Phytochemical	All-trans-retinoic acid
Drug	PI3K inhibitor
Disease Info	[ICD-11: 2D4Y]	Adenoid cystic carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	We displayed the morphologically and genetic featured PDXs which recapitulated the heterogeneity of original ACC tumors, indicating that the models could be used as a platform for drug screening for therapy response. The feasibility of combination treatment approaches for dual targets were confirmed, providing new regimens for personalized therapies in ACC.

Pair Name	Silibinin, Sorafenib
Phytochemical	Silibinin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	These results suggested that silibinin improved the efficacy of sorafenib in HCC therapy, indicating a clinical promising therapeutic strategy for HCC patients.

Pair Name	Sulforaphane, Gefitinib
Phytochemical	Sulforaphane
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	SFN overcame T790M-mediated gefitinib resistance in vitro through EMT. Thus, a combination of gefitinib and SFN may be a beneficial treatment strategy for lung cancer patients with acquired resistance due to T790M mutation.

Pair Name	Sulforaphane, Lapatinib
Phytochemical	Sulforaphane
Drug	Lapatinib
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Therapeutic Mechanism of Lapatinib Combined with Sulforaphane on Gastric Cancer

Pair Name	Sulforaphene, Carboplatin
Phytochemical	Sulforaphene
Drug	Carboplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	This study demonstrates that the duel character of this combination therapy may be an effective replacement for conventional therapy alone against NSCLC.

Pair Name	Sulforaphene, Photodynamic therapy
Phytochemical	Sulforaphene
Drug	Photodynamic therapy
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer.

Pair Name	Tangeretin, Metformin
Phytochemical	Tangeretin
Drug	Metformin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The current work underscores the importance of metformin as an ERMA in tackling breast cancer and as a novel approach to boost its anticancer activity via a synergistic combination with tangeretin.

Pair Name	Trigonelline, Cisplatin
Phytochemical	Trigonelline
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Our study demonstrated that Trigonelline blocks Nrf2 activation and its nuclear translocation via inhibition of EGFR signalling pathway. It has improved responsiveness of NSCLC cells for Cisplatin and Etoposide and could be a promising choice for lung cancer therapy. Toxicol In Vitro. 2021 Feb;70:105038. doi: 10.1016/j.tiv.2020.105038.

Pair Name	Ursodiol, Sorafenib
Phytochemical	Ursodiol
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The present findings may represent a promising therapeutic strategy for patients with advanced hepatocellular carcinoma.

Pair Name	Usnic acid, Sorafenib
Phytochemical	Usnic acid
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Expression
Result	Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid

Pair Name	Epigallocatechin gallate, Gefitinib
Phytochemical	Epigallocatechin gallate
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	EGCG overcomes Gef resistance by inhibiting autophagy and augmenting cell death through targeting ERK pathway in NSCLC. Gef and EGCG combination therapy may be an effective strategy to overcome acquired resistance in NSCLC.

Pair Name	Epigallocatechin gallate, Osimertinib
Phytochemical	Epigallocatechin gallate
Drug	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	The combined use of EGFR-TKIs and EGCG significantly reversed the Warburg effect by suppressing glycolysis while boosting mitochondrial respiration, which was accompanied by increased cellular ROS and decreased lactate secretion. The combination effectively activated the AMPK pathway while inhibited both ERK/MAPK and AKT/mTOR pathways, leading to cell cycle arrest and apoptosis, particularly in drug-resistant NSCLC cells. The in vivo results obtained from mouse tumor xenograft model confirmed that EGCG effectively overcame osimertinib resistance.

Pair Name	Honokiol, Paclitaxel
Phytochemical	Honokiol
Drug	Paclitaxel
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction

Pair Name	Oleanolic Acid, Cisplatin
Phytochemical	Oleanolic Acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	OLO-2 treatment also exhibited up to 4.6-fold selectivity against human lung adenocarcinoma cells. Taken together, the results of the present study shed light on the drug resistance-reversing effects of OLO-2 in lung cancer cells.

Pair Name	Platycodin D, Histone deacetylase inhibitor
Phytochemical	Platycodin D
Drug	Histone deacetylase inhibitor
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Platycodin D reverses histone deacetylase inhibitor resistance in hepatocellular carcinoma cells by repressing ERK1/2-mediated cofilin-1 phosphorylation

Pair Name	Rosmarinic acid, Cisplatin
Phytochemical	Rosmarinic acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Activity
Result	Rosmarinic acid reverses non-small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway

Pair Name	Scutellarin, Cisplatin
Phytochemical	Scutellarin
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	This study identifies the unique role of scutellarin in reversing cisplatin resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.

Pair Name	Shikonin, Gefitinib
Phytochemical	Shikonin
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	Shikonin-induced cell apoptosis is closely associated with ROS elevation in the cells. These findings indicate that Shikonin can be an effective small molecule treating gefitinib-resistant NSCLC.

Pair Name	Shogaol, TNF-related apoptosis inducing ligand
Phytochemical	Shogaol
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 1		Phosphorylation
Result	This study gives rise to the possibility of applying shogaol as an antitumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant colon tumor therapy.