Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis

Table 3

Potential mechanisms of action of phytocompounds in pancreatitis.

Apoptosis
↑ apoptosis	↑ apoptosis (index) of pancreatic acinar cells	Artemisinin [89], baicalin [92, 93], crambene [51, 95], embelin [7], emodin [113], hesperidin [117, 118], ligustrazine [119], magnolol [117], naringin [117, 118], nordihydroguaiaretic acid [122], rhein [53, 117], rutin [132]
	↑ Bax protein	Baicalin [91, 93]
	↑ caspase-3	Artemisinin [89], baicalin [92], crambene [51], curcumin [96, 98], embelin [7], ligustrazine [119], rhein [53]
	Cytochrome C	Rhein [53]
	↑ p53	Ligustrazine [119], rhein [53]
	↓ Bcl-2 protein renal	Baicalin [91]
	↓ p38	Ligustrazine [119]
	↑ Bax protein	Baicalin [91, 93]
	↑ Bax/Bcl-2 ratio	Rhein [53]
	↑ caspase-8, -9	Crambene [51], embelin [7]
	↑ renal apoptotic indexes	Baicalin [91]
	↓ calcium overload in the cytoplasm	Emodin [113]
	↓ ER stress transducers	Emodin [113]
	Modulates the posttranslational modifications of histone H3	Nordihydroguaiaretic acid [122]
↓ apoptosis	↑ Bcl-2	Resveratrol [127]
	↑ mRNA expression of CARD	Rutin [134]
	↓ apoptosis of intestinal mucosa cells	Emodin [112]
	↓ Bax	Resveratrol [127]
	↓ caspase-1	Rutin [133, 134]
	↓ caspase-3, -8, -9, -12	Grape seed proanthocyanidins [214]
	↓ caspases-3 expressions in brain	Resveratrol [127]
	↓ PYD	Rutin [134]
Inflammation
Inflammation markers	↓ CRP	Emodin [115], rutin [132]
Inflammation activators	↓ AP-1	Curcumin [98], curcumin [100]
	↓ ASC-NLRP3	Rutin [133]
	↓ Erk	Ligustrazine [119]
	↓ IκB degradation	Curcumin [100]
	↓ MCP-1	Crambene [95]
	↓ MIP-1α protein	Artemisinin [89]
	↓ NAP78	Curcumin [96]
	↓ NF-κB (activation)	Artemisinin [89], curcumin [97–100], dihydroresveratrol [129, 130], emodin [107, 108], grape seed proanthocyanidins [214], nordihydroguaiaretic acid [122], resveratrol [123, 125]
	↓ phosphorylated p38	Nordihydroguaiaretic acid [122]
	↓ PKCα	Breviscapine [215]
	↓ TLR4 expression in pancreas	Curcumin [97] emodin + baicalin [44]
Inflammation inhibitors	↑ Nrf2	Grape seed proanthocyanidins [214]
	↑ PPARγ	Curcumin [99]
	↑ IL-10	Crambene [95]
	↑ ratio IL-10/ IFN-γ  & ratio of myeloid/lymphoid dendritic cells	Magnolol [121]
Promoting phagocytosis of apoptotic neutrophils	↑ ICAM-3 and mCD14 expression in pMΦs	Emodin [109, 110]
Inflammation mediators	↓ chemokine	Curcumin [98, 100]
	↓ cytokines	Rutin [133]
	↓ ET-1	Baicalin [91], baicalin [94]
	↓ ICAM-1 and VCAM-1 expression in the intestine	Resveratrol [126]
	↓ IFN-γ	Grape seed proanthocyanidins [214]
	↓ IL-18	Rutin [133, 134]
	↓ IL-1β	Artemisinin [89], crambene [95], dihydroresveratrol [129], emodin [107, 108], grape seed proanthocyanidins [214], ligustrazine [119], rutin [133]
	↓ IL-6	Baicalin [91], curcumin [98, 100], dihydroresveratrol [129], emodin [104, 105, 108], emodin + baicalin/baicalein [44, 114], ligustrazine [119], rhein [131], rutin [132, 134]
	↓ IL-8	Resveratrol [123]
	↓ PLA2	Baicalin [91, 94]
	↓ P-selectin	Baicalin [92, 94]
	↓ TNF-α	Baicalin [91–93], crambene [95], curcumin [96–101], emodin [104, 105, 107, 108, 111, 115], emodin + baicalin/baicalein [44, 114], grape seed proanthocyanidins [214], ligustrazine [119], nordihydroguaiaretic acid [122], resveratrol [123, 126], rhein [131], rutin [134]
	↓ WBC count	Curcumin [101], rutin [134]
Nitrosative stress
Nitrosative enzymes	↓ iNOS	Curcumin [98, 100]
	↓ iNOS in pMΦs	Resveratrol [125]
Nitrosation products	↓ NO	Baicalin [91, 94], curcumin [98, 101], Hesperidin [116]
	↓ 3-nitrotyrosine	Rutin [132]
Oxidative stress
Oxidative enzymes	↓ MPO	Artemisinin [89], curcumin [96], dihydroresveratrol [130], emodin [105, 115], ligustrazine [119], nordihydroguaiaretic acid [122], rhein [131], rutin [132, 133]
	↓ MPO hepatic	Emodin [115]
Protective antioxidant enyzmes/mechanisms	↑ GPx	Rutin [133]
	↑ catalase	Resveratrol [124], rutin [132, 133]
	↑ HO-1	Grape seed proanthocyanidins [214]
	↑ SOD	Emodin [108], nordihydroguaiaretic acid [122], resveratrol [126, 128], rutin [132, 133]
	↑ GSH	Nordihydroguaiaretic acid [122]
Oxidation products	↓ HO^∙	Curcumin [101]
	↓ lipid hydroperoxides	Rutin [133]
	↓ LPO	ligustrazine [120]
	↓ MDA	Emodin [108, 115], resveratrol [126, 128], rutin [132]
	↓ oxidative stress index	Rutin [133]
	↓ protein carbonyls	Curcumin [96]
	↓ ROS generation	Hesperidin [116, 117], magnolol [117], naringin [117, 118], rhein [117]
	↓ TBARS	Nordihydroguaiaretic acid [122], rutin [133]
	↓ pancreatic fgl-2	Curcumin [96]
	↓ Pancreatic inflammation (pancreatic release of IL-1β and IL-6)	Artemisinin [90]
Protection against injury	↑ heat shock proteins	Nordihydroguaiaretic acid [122]
Blood flow	↑ pancreatic blood flow	Emodin [102]
	↑ 6-keto-PGF1α	Emodin [102, 103], ligustrazine [120]
	↑ PGE2	Emodin [102, 103]
	↓ AngII	Emodin [115]
	↓ TXB2	Emodin [102], emodin [103], ligustrazine [120]
Pancreatic fibrosis	Pancreatic fibrosis Ł ↑ TGF-β1	Crambene [95], emodin [106]
	Pancreatic fibrosis Ł ↓ collagen, fibronectin, laminin, pancreatic fibrosis	Emodin [106]
Lung
Lung inflammatory activators	↓ NF-κB	Dihydroresveratrol [129]
	↓ TLR4 expression	Emodin + baicalin/baicalein [44]
	↓ TNF-α	Curcumin [101]
	↓ IL-1β, IL-6	Dihydroresveratrol [129]
	↓ pulmonary	Dihydroresveratrol [129]
	↓ TNF-α lung	Curcumin [101], dihydroresveratrol [129], rhein [131]
Lung nitrosative stress	↓ iNOS lung	Curcumin [101]
Lung function	↓ lung hyperreactivity	Curcumin [101]
	↑ claudin-4	Emodin [105]
	↑ claudin-5	Emodin [104, 105]
	↑ occludin	Emodin [104, 105]
	↑ AQP1 and AQP5 in lung	Emodin [111]
Bowel
Bowel injury	↓ bacteria and endotoxin translocation	Emodin [112]
	↓ ICAM-1 and VCAM-1 expression in the intestine	Resveratrol [126]