SUPPLEMENTARY DATA Supplementary table 1

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Chemical species. Murraya koenigii. Piper betle. Mentha spicata. Glycosides. +. +. +. Terpenoid. +. +. +. Tannin. +. +. +. Steroid. +. +. +. Anthraquinone. +. +. +.
SUPPLEMENTARY DATA Supplementary table 1: Preliminary phytochemical analysis Chemical species Glycosides Terpenoid Tannin Steroid Anthraquinone Phenolic Flavonoid Alkaloid Saponin Carbohydrate Protein

Murraya koenigii + + + + + + + + + + +

Piper betle + + + + + + + + + + +

Mentha spicata + + + + + + + + + + +

Supplementary table 2: Identified phytochemicals in Murraya koenigii (L.) Sprengel using GC-MS corresponding to Fig. 2 Compound name

Formula

[M-H]-

3-Hydroxymethyl-2trimethylsilyloxypentane

C9H22O2Si

189

D-Limonene

C10H16

135

Lactic acid, bis-TMS

C9H22O3Si2

233

Caproic acid, TMS

C9H20O2Si

187

Undecane

C11H24

155

Neodihydrocarveol

C10H18O

153

trans-Dihydrocarvone

C10H16O

151

Benzaldehyde, 2,5dimethylPulegone

C9H10O

133*

C10H16O

151

Carvone

C10H14O

149

Nerol, trimethylsilyl ether

C13H26OSi

225

Octanoic acid, TMS ester

C11H24O2Si

215

Phosphoric acid, trisTMS

C9H27O4PSi3

313

Identifying mass fragments 117* (C6H13O2), 75 (C2H2OSi) 93 (C7H9), 68* (C5H8) 147 (C5H11O3Si), 117 (C5H13OSi), 73* (C3H9Si) 117 (C6H13O2), 73* (C2H7OSi) 71 (C5H11), 57* (C4H9) 107 (C8H11), 93* (C7H9) 95 (C6H7O), 65* (C5H7) 105 (C8H9)

Retention time (min) 5.79

% abundance

8.38

2.264

109 (C7H9O), 81* (C6H9) 93 (C6H5O), 82* (C5H6O), 54 (C4H6) 121 (C9H13), 73 (C3H9Si) 201 (C10H21O2Si), 117 (C4H9O2Si), 75 (C2H7OSi) 229 (C8H24O4PSi3),

0.059

9.43 0.261 9.61

0.074

10.39

0.046

13.02

0.648

13.09

0.545

13.58

0.396

14.28

0.120

14.40 7.795 14.85

0.783

14.97 0.107 15.60

1.654

Tridecane

C13H28

183

3-Eicosene, (E)-

C20H40

279

2-Isopropyl-5-methyl-1heptanol

C11H24O

171

Decane, 2,3,5,8tetramethyl-

C14H30

3,5-Heptadienal, 2ethylidene-6-methyl-

C10H14O

149

Nonanoic acid, trimethylsilyl ester

C12H26O2Si

229

Caryophyllene

C15H24

203

Decanoic acid, trimethylsilyl ester

C13H28O2Si

243

4-Allyl-2methoxyphenoxy, TMS

C13H20O2Si

Phenol, 3,5-bis(1,1dimethylethyl)-

C14H22O

205

Tetradecane, 2,6,10trimethyl-

C17H36

239

Isopropyl laurate

C15H30O2

Lauric acid (TMS)

C15H32O2Si

197

235

241

271

73 (C3H9Si) 71 (C5H11), 57* (C4H9) 69 (C5H9), 57 (C4H9) 85 (C5H9O), 57* (C4H9) 85 (C6H13), 71 (C5H11), 57* (C4H9) 107* (C8H11), 79 (C5H3O) 215* (C11H23O2Si), 129 (C5H9O2Si), 133 (C10H13), 93* (C7H9) 229* (C12H25O2Si), 117 (C4H9O2Si) 206* (C11H14O2Si), 179 (C9H1O2Si), 191* (C13H19O), 57 (C4H9) 85 (C6H13), 71 (C5H11), 57* (C4H9) 183 (C12H23O), 102 (C5H10O2), 60* (C3H8O) 257 (C14H29O2Si),

15.87

0.158

16.05

0.173

16.28 0.170 16.58 0.158 17.04

0.048

17.56 0.034 19.15

0.051

20.03 0.046 20.25 0.065 21.33

0.114

22.01 0.461 24.01 0.278 24.64

0.391

Azelaic acid, bis-TMS

Myristic acid, trimethylsilyl ester

Pentadecanoic acid, TMS ester

Palmitelaidic acid, trimethylsilyl ester

Palmitic acid, TMS

Margarate, TMS

Linoleic acid, TMS

α-Linolenic acid, TMS

Stearic acid, trimethylsilyl ester

C15H32O4Si2

C17H36O2Si

C18H38O2Si

C19H38O2Si

C19H40O2Si

C20H42O2Si

C21H40O2Si

C21H38O2Si

C21H44O2Si

331

299

313

325

327

341

351

349

355

117* (C4H9O2Si) 201 (C10H21O2Si), 73* (C3H9Si) 285 (C16H33O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 299 (C17H35O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 311 (C18H35O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 313 (C18H37O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 327 (C19H39O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 337 (C20H37O2Si), 73* (C3H9Si) 335 (C20H35O2Si), 129 (C5H9O2Si), 73 (C3H9Si) 341 (C20H41O2Si), 117 (C4H9O2Si),

27.88 0.427 28.85 2.833 30.81 0.364 32.20 0.514 32.73 17.939 34.49 0.562 35.69 8.473 35.84 20.738 36.26 17.223

Eicosanoic acid, TMS ester

Bumetrizole

C23H48O2Si

C17H18ClN3O

Docosanoic acid, TMS ester

C25H52O2Si

Squalene

C30H50

Heptacosane

Stigmasterol, TMS

β-Sitosterol TMS

C27H56

C32H56OSi

C32H58OSi

383

314

411

409

379

483

485

73* (C3H9Si) 369 (C22H45O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 300* (C16H15ClN3O), 272 (C15H15ClN3), 120 (C7H6NO) 397 (C24H49O2Si), 117* (C4H9O2Si) 95 (C7H11), 81 (C6H9), 69* (C5H9) 85 (C6H13), 71 (C5H11), 57 (C4H9) 255 (C19H27), 129 (C6H13OSi), 83* (C6H11) 396* (C29H48), 81 (C5H5O)

39.47 2.008 41.19

0.434 42.49 0.522 45.17 2.601 48.70 2.121 52.02 1.612 53.17

4.731

Supplementary table 3: Identified phytochemicals in Piper betle L. using GC-MS corresponding to Fig. 2 Compound name

Formula

[M-H]-

Eugenol

C10H12O2

163*

(-)-β-Bourbonene

C15H24

203

Methyleugenol

C11H14O2

177*

Caryophyllene

C15H24

203

β-copaene

C15H24

203

Humulene

C15H24

203

4-Allyl-2methoxyphenoxy, TMS

C13H20O2Si

235

γ-Muurolene

C15H24

203

Phenol, 2,4-bis(1,1dimethylethyl)-

C14H22O

205

Cubedol

C15H26O

221

Eugenol acetate

Nonadecane

C12H14O3

C19H40

205

267

Identifying mass fragments 149 (C9H9O2), 131 (C9H7O) 161 (C12H17), 123 (C9H15), 81* (C6H9) 163 (C10H11O2), 147 (C10H11O) 133 (C10H13), 93* (C7H9) 161* (C12H17), 105 (C8H9) 121 (C9H13), 93 (C7H9) 206* (C11H14O2Si), 179 (C9H1O2Si),

Retention time (min) 17.82

% abundance

161* (C12H17), 69 (C10H15) 191* (C13H19O), 57 (C4H9) 161 (C12H17), 119 (C9H11), 105 (C8H9) 164* (C10H12O2), 149 (C9H9O2) 85 (C6H13), 71 (C5H11), 57* (C4H9)

20.55

1.046

21.32

0.564

33.854

18.25 8.046 18.63

3.815

19.14

0.636

19.38

1.203

20.00

0.082

20.24 3.480

21.51 0.144 21.70 0.260 23.36 0.636

1-Buten-3-one, 1-(2carboxy-4,4dimethylcyclobutenyl)-

C11H14O3

Isopropyl laurate

C15H30O2

Lauric acid (TMS)

Palmitic acid, methyl ester

Palmitic acid, TMS

C15H32O2Si

C17H34O2

C19H40O2Si

193

241

271

269

327

Phytol

C20H40O

295

1-Trimethylsiloxy3,7,11,15-tetramethyl2-hexadecene

C23H48OSi

367

Oleic acid, trimethylsilyl ester

C21H42O2Si

Squalene

Heptacosane

C30H50

C27H56

353

409

379

179 (C10H11O3), 151 (C8H7O3), 105 (C8H9) 183 (C12H23O), 102 (C5H10O2), 60* (C3H8O) 257 (C14H29O2Si), 117* (C4H9O2Si) 227 (C14H27O2), 143 (C8H15O2), 87 (C4H7O2), 74 (C3H6O2) 313 (C18H37O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 123 (C9H15), 71* (C4H7O) 143* (C7H15OSi), 123 (C9H15), 73 (C3H9Si) 339 (C20H39O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 95 (C7H11), 81 (C6H9), 69* (C5H9) 85 (C6H13), 71 (C5H11), 57 (C4H9)

23.89 0.762 24.00 0.882 24.64 0.978 30.33 0.766 32.69 4.218 33.90

21.299

35.09 12.258 35.75 0.253 45.17 2.868 48.69 1.316

Vitamin E

Ethyl iso-allocholate

C29H50O2

C26H44O5

429

435

205 (C13H17O2), 164* (C10H13O2) 400 (C26H40O3), 253 (C11H19O2), 81 (C20H35O5), 69 (C4H5O), 55* (C3H3O)

49.31 0.458 50.51

0.178

Supplementary table 4: Identified phytochemicals in Mentha spicata L. using GC-MS corresponding to Fig. 2 Compound name

Formula

[M-H]-

d-α-Pinene

C10H16

135

Sabinen

C10H16

135

Terpinolen

C10H16

135

γ-Terpinene

C10H16

135

cis-4-methoxy thujane

Terpinen-4-ol

Benzaldehyde, 2,4dimethylα-Terpineol

β-Elemen

Caryophyllene

Humulene

C11H20O

C10H18O

167

153

C9H10O

133*

C10H18O

153

C15H24

C15H24

C15H24

203

203

203

Identifying mass fragments 125 (C9H13), 93* (C7H9), 77 (C6H5) 93 (C7H9), 77 (C6H5) 121 (C9H13), 93* (C7H9) 121 (C9H13), 93* (C7H9), 77 (C6H5) 153 (C10H17O), 125 (C8H13O), 93 (C7H9) 111 (C7H11O); 93 (C7H9); 71 (C4H7O) 105 (C8H9)

Retention time (min) 5.95

212 (C9H13), 93 (C7H9), 59* (C3H7O), 147 (C11H15), 107 (C8H12), 81* (C6H9) 133 (C10H33), 93* (C7H9), 81 (C6H9) 121 (C9H13), 93 (C7H9)

13.71

% abundance 0.692

6.92

3.258

8.04

0.113

9.19 0.181 10.26 1.242 12.55 0.068 13.58

0.136

0.159 18.41 8.926 19.22 32.165 20.03

13.511

α-Selinene

C15H24

203

Decane, 2,3,5,8tetramethyl-

C14H30

197

2-Methylhexadecan-1ol

C17H36O

255

Caryophyllene oxide

C15H24O

219

Hexadecane

C16H34

225

Humulene epoxide 2

C15H24O

219

Isopropyl laurate

Globulol

C15H30O2

C15H26O

241

221

Heptadecane, 2,6,10,15-tetramethyl-

C21H44

295

3,7,11,15-Tetramethyl2-hexadecen-1-ol

C20H40O

295

Hexahydrofarnesyl acetone

C18H36O

267

Hexadecanoic acid, methyl ester

C17H34O2

269

189* (C14H21), 107 (C8H11), 81 (C6H9), 85 (C6H13), 71 (C5H11), 57* (C4H9) 69 (C5H9), 57* (C3H5O) 121 (C9H13), 93 (C7H9), 79* (C6H7) 71 (C5H11), 57 (C4H9) 138 (C9H14O), 109* (C8H13), 96 (C6H8O) 183 (C12H23O), 102 (C5H10O2), 60* (C3H8O) 161 (C12H17), 109 (C8H13), 69* (C5H9) 71 (C5H11), 57* (C4H9) 123 (C8H11O), 95 (C7H11), 81* (C6H9) 71 (C5H11), 58* (C3H6O) 143 (C8H15O2), 87 (C4H7O2), 74* (C3H6O2)

21.05 3.672 22.00 0.327 22.25

0.136

23.16 0.314 23.37

0.149

23.77 0.074 24.00 0.589 24.79 1.210 26.81

0.220

28.59 0.751 28.71

0.159

30.32 0.411

Isophytol

C20H40O

295

Palmitic acid, TMS

C19H40O2Si

327

Phytol

C20H40O

296

1-Heptatriacotanol

C37H76O

356

Pentan-2-one, 4-(2fluorenylimino)-

C18H17NO

262*

2-(4-Methoxyphenyl)-7methyl-5-oxo-3,5dihydroindolizine-6carbonitrile Squalene

C17H14N2O2

277*

1-(3-Methoxy-2nitrobenzyl)isoquinoline

Heptacosane

C30H50

C17H14N2O3

C27H56

Retinoic acid, 5,6epoxy-5,6-dihydro-

C20H28O3

Campesterol

C28H48O

409

293

379

315

399

278 (C20H38), 71* (C4H7O) 313 (C18H37O2Si), 117 (C4H9O2Si), 73* (C3H9Si) 123 (C9H15), 71* (C4H7O) 69 (C5H9), 55* (C4H7), 165 (C13H9), 84 (C4H6NO) 263 (C16H11N2O2), 89 (C7H5)

30.76

95 (C7H11), 81 (C6H9), 69* (C5H9) 248* (C17H14NO), 233 (C16H11NO), 127 (C9H5N) 85 (C6H13), 71 (C5H11), 57 (C4H9) 271 (C19H27O), 159 (C11H11O), 91* (C7H7) 289 (C21H37), 213 (C16H21), 55* (C3H3O)

45.16

0.104

32.68 0.081 33.88

1.281

40.33

0.155

40.51

0.052

44.68 9.631

1.660 47.78

12.689 48.70 1.944 49.17 0.696 50.85 0.281

Stigmasterol

β-Sitosterol

C29H48O

C29H50O

411

413

255 (C19H27), 83 (C5H7O), 55* (C4H7) 303 (C22H39), 213 (C16H21), 107 (C8H11), 55* (C3H3O)

51.42 0.731 52.49 2.232

Supplementary Table 5: Represents IC50 values (μg/mL) and dose-dependent inhibitory correlations of M. koenigii, P. betle and M. spicata M. koenigii

DPPH

P. betle

P value

rp

r2

IC50

P value

rp

r2

IC50

P value

rp

r2

IC50

P value

rp

r2

107.48±6.5

0.0056

0.937

0.879

36.76±3.

0.0193

0.884

0.781

241.51±1

0.0033

0.952

0.907

9.49±0.82

0.0975

0.732

0.537

0.0007

0.978

0.956

4.32±0.43

41 0.0649

0.783

0.614

7.41±0.4

5.89 0.0667

0.780

0.609

5 ABTS● Hydroxyl

0.869

0.755

21

117.51±10.02 (ascorbic acid)

0.991

0.982

---

0.0036

0.882

0.779

---

0.0005

0.938

0.881

---

0.0001

0.996

0.992

568.34±55.

0.0010

0.973

0.947

268.99±1

0.0187

0.885

0.784

402.18±7

0.0010

0.973

0.947

597.15±11.90

0.0007

0.977

0.955

0.0366

0.901

0.812

0.0007

0.977

0.954

0.0037

0.949

0.901

358.72±33.

2.44 0.0103

0.957

0.917

150.37±4.8

18189.36± 1305.49

222.50±1

.65 0.0015

0.988

0.976

6.98 0.0068

0.931

0.868

7 Hydrogen peroxide

0.0246

0.0001

66 Nitric oxide

13.14±0.

(ascorbic acid)

---

00 Superoxide

Standard

IC50

0 TAA

M. spicata

75.09±12

0.963

0.928

4289.58± 430.96

0.0461

0.884

0.782

129.58 0.7975

0.057

0.636

.83 0.0019

1546.33±

(mannitol)

148.88±6

(quercetin) 0.0053

0.939

0.883

.18 0.0066

0.932

0.870

18189.88 ±1308.70

121.41±5.72

101.62±4.74 (curcumin)

0.0004

0.982

0.964

3176.62±148. 04 (sodium pyruvate

Peroxynitrite

Singlet oxygen

2107.80±1

0.0000

9.36

3

493.12±19.

0.0005

0.987

0.975

35.28±1.96

0.0006

0.979

0.958

120.85 0.981

0.962

39 Hypochlorous acid

2077.69±

293.70±9

0.983

0.967

34.36±4.

0.0001

0.990

0.980

68.89±15.7

0.035

0.842

0.710

7 Ferrous chelation

Reducing power

193.01±4

0.0015

0.967

0.936

0.0000

7.58

5

---

0.0009

0.994

0.974

0.988

0.949

0.954

589.88±3

34.36±4.

0.0001

0.989

0.978

115.39±2

0.0002

0.988

0.976

5.545E

.18

-005

---

9.147E -005

0.993

0.992

0.987

0.984

0.0013

0.969

0.940

0.0004

0.981

0.964

165.91±16.31

0.0000

0.995

0.991

(ascorbic acid)

2

11.11±0.22

0.0062

0.934

0.873

1.45±0.04

0.0000

0.981

0.962

(EDTA)

9

---

0.0004

0.981

0.964

195.94±6.71 (lipoic acid)

0.0002

0.986

0.973

0.0036

0.950

0.903

2.63

203.73±6

734.81±25.31 (gallic acid)

37

0.74

1077.22±6

0.977

7.91

37 Lipid peroxidation

0.0007

116.18

.34 0.0003

2208.34±

(Trolox)

887.50±4

0.0000

4.54

5

---

0.0005

0.993

0.981

0.987

0.963

(ascorbic acid)

P>0.05 is considered significant; r = Pearson’s correlation coefficient and r2 = coefficient of determination (linear regression).

Supplementary Figures

Supplementary Table 6: Binding affinities of selected phytochemicals with two major antioxidant transcription factor (Nrf2 and FOXO3) proteins and their ADME (absorption, distribution, metabolism, and excretion) profiling based on ‘Lipinski's rule of 5’ Binding Affinity (kcal/mol) Compounds

Molecular mass (Dalton)

Log P

hydrogen bond donors

hydrogen bond acceptors

Molar refractivity

136

3.30

0

0

45.91

Nrf2 (5FNQ) -5.8

FOXO3 (2UZK) -5.7

Carvone

-5.9

-5.1

150

2.48

0

1

46.30

Linolenic Acid

-4.1

-3.3











Squalene

-7.0

-5.8

410

10.60

0

0

140.06

Stigmasterol

-6.9

-5.5

412

7.80

1

1

128.12

β-Sitosterol

-7.2

-5.1

414

8.02

1

1

128.21

Eugenol

-5.9

-5.6

164

2.12

1

2

48.55

Phytol

-2.5

-3.3











Pinene

-5.6

-5.3

136

2.99

0

0

43.75

β-Elemene

-7.0

-5.6

204

4.74

0

0

68.76

Humulene

-7.1

-5.1

204

5.03

0

0

68.90

Caryophyllene

-2.3

-2.1











D-Limonene